PAPER III

UNIT-5

RECENT TRENDS IN
TREATMENT
MODALITIES OF BREAST
CANCER

Content

UNIT

CONTENT
HORMONAL THERAPY
TARGETED THERAPY

ENDOCRINE THERAPY

BONE DETECTECTION THERAPY

CHEMOTHERAPY
RADIATION THERAPY
SURGICAL PROCEDURES-BREAST RECONSTRUCTIVE
SURGERIES
COMPLEMENTARY & ALTERNATIVE THERAPIES

GENERAL OBJECTIVES

At the end of the class doctoral student will be able to Explain recent trends in
treatment modalities of breast cancer and develop desirable skills while practising in
clinical area.
SPECIFIC OBJECTIVES
At end of this chapter doctoral student will be able to
Explain About Hormonal Therapy
Brief About Targeted Therapy
Discuss About Endocrine Therapy.
Enumerate About Bone Detected Therapy
List Down The Classification Of Chemotherapy
Narrate About The Radiation Therapy
Enlist About Surgical Procedures-Breast Reconstructive Surgeries
Discuss About Complementary & Alternative Therapies

BREAST CANCER: TREATMENT OPTIONS

INTRODUCTION

Breast treatment takes different approaches depending on the conditions. The

mainstay of breast cancer treatment is surgery when the tumor is localized, followed
by chemotherapy (when indicated), radiotherapy, and, for ERpositive tumours, adjuvant hormonal therapy (with tamoxifen or an aromatase
inhibitor). Management of breast cancer is undertaken by a multidisciplinary team
based on national and international guidelines. Depending on clinical criteria (age,
type of cancer, size, presence or absence of metastasis) patients are roughly divided
to high risk and low risk cases, with each risk category following different rules for
therapy. Treatment possibilities include radiation therapy, chemotherapy, hormone
therapy, and immune therapy.1
1.HORMONAL THERAPY
Hormone therapy is another form of systemic therapy. It is most often used as an
adjuvant therapy to help reduce the risk of the cancer coming back after surgery, but
it can be used as neo adjuvant treatment, as well.
A woman's ovaries are the main source of the hormone oestrogen until menopause.
After menopause, smaller amounts are still made in the body's fat tissue, where a
hormone made by the adrenal gland is converted into oestrogen.
Oestrogen promotes the growth of cancers that are hormone receptor-positive. About
2 out of 3 of breast cancers are hormone receptor-positive they contain receptors
for the hormones estrogens (ER-positive cancers) and/or progesterone (PR-positive
cancers). Most types of hormone therapy for breast cancer either lower oestrogen
levels or stop oestrogen from acting on breast cancer cells. This kind of treatment is
helpful for hormone receptor-positive breast cancers, but it does not help patients
whose tumors are hormone receptor negative (both ER- and PR-negative).

Hormonal therapy medicines treat hormone-receptor-positive breast cancers in two

ways:1

By Lowering The Amount Of The Hormone Oestrogen In The Body

By Blocking The Action Of Oestrogen On Breast Cancer Cells

1.1.How do hormones stimulate the growth of breast cancer?

Hormone-sensitive breast cancer cells contain proteins known as hormone receptors
that become activated when hormones bind to them. The activated receptors cause
changes in the expression of specific genes, which can lead to the stimulation of cell
growth.
To determine whether breast cancer cells contain hormone receptors, doctors test
samples of tumor tissue that have been removed by surgery. If the tumor cells contain
estrogen receptors, the cancer is called estrogen receptor-positive (ER-positive),
estrogen-sensitive, or estrogen-responsive. Similarly, if the tumor cells contain
progesterone receptors, the cancer is called progesterone receptor-positive (PR- or
PgR-positive). Approximately 70 percent of breast cancers are ER-positive. Most
ER-positive breast cancers are also PR-positive .
Breast cancers that lack estrogen receptors are called estrogen receptor-negative (ERnegative). These tumors are estrogen-insensitive, meaning that they do not use
estrogen to grow. Breast tumors that lack progesterone receptors are called
progesterone receptor-negative (PR- or PgR-negative).1
1.2Types Of Hormone Therapy Used For Breast Cancer
Several strategies have been developed to treat hormone-sensitive breast cancer,
including the following:

 Blocking ovarian function: Because the ovaries are the main source of estrogen in
premenopausal women, estrogen levels in these women can be reduced by eliminating
or suppressing ovarian function. Blocking ovarian function is called ovarian
ablation.Ovarian ablation can be done surgically in an operation to remove the ovaries
(calledoophorectomy) or by treatment with radiation. This type of ovarian ablation is
usually permanent. Alternatively, ovarian function can be suppressed temporarily by
treatment with drugs called gonadotropin-releasing hormone (GnRH)

agonists,

which are also known as luteinizing hormone-releasing hormone (LH-RH) agonists.

These medicines interfere with signals from the pituitary gland that stimulate the
ovaries to produce estrogen.Examples of ovarian suppression drugs that have been
approved by the U.S. Food and Drug Administration (FDA) are goserelin (Zoladex)
and leuprolide (Lupron).

Blocking estrogen production: Drugs called aromatase inhibitors can be used to

block the activity of an enzyme called aromatase, which the body uses to make estrogen
in the ovaries and in other tissues. Aromatase inhibitors are used primarily in post
menopausalwomen because the ovaries in premenopausal women produce too much
aromatase for the inhibitors to block effectively. However, these drugs can be used in
premenopausal women if they are given together with a drug that suppresses ovarian
function.Examples of aromatase inhibitors approved by the FDA
are anastrozole (Arimidex) andletrozole (Femara), both of which temporarily inactivate
aromatase, and exemestane(Aromasin), which permanently inactivates the enzyme.
Blocking estrogens effects: Several types of drugs interfere with estrogens ability
to stimulate the growth of breast cancer cells:1
Selective estrogen receptor modulators (SERMs) bind to estrogen receptors,
preventing estrogen from binding. Examples
of SERMs approvedbytheFDAaretamoxifen (Nolvadex), raloxifene (Evista),
and toremifene (Fareston). Tamoxifen has been used for more than 30 years to treat

hormone receptor-positive breast cancer.

Because SERMs bind to estrogen receptors, they can potentially not only block
estrogen activity (i.e., serve as estrogen antagonists) but also mimic estrogen effects
(i.e., serve as estrogen agonists). Most SERMs behave as estrogen antagonists in
some tissues and as estrogen agonists in other tissues. For example, tamoxifen
blocks the effects of estrogen in breast tissue but acts like estrogen in the uterus and
bone.
Other antiestrogen drugs, such as fulvestrant (Faslodex), work in a somewhat
different way to block estrogens effects. Like SERMs, fulvestrant attaches to the
estrogen receptor and functions as an estrogen antagonist. However, unlike SERMs,
fulvestrant has no estrogen agonist effects. It is a pure antiestrogen. In addition,
when fulvestrant binds to the estrogen receptor, the receptor is targeted for
destruction.1

Aromatase inhibitors
Although women who have had their menopause don't produce oestrogen from their
ovaries, a small amount is made in body fat. Aromatase inhibitors block this
oestrogen from being made. So these drugs are used for women who've had their
menopause. You take them as tablets once a day. There is information below about
Aromatase inhibitors for early breast cancer
Aromatase inhibitors to prevent breast cancer1

Aromatase inhibitors for early breast cancer

Doctors can use the aromatase inhibitors anastrozole, exemestane or letrozole to treat
women with early breast cancer, who have had their menopause. Aromatase
inhibitors can also treat breast cancer that has spread.

Anastrozole (Arimidex) has been tested after surgery for early breast cancer. It works
as well as tamoxifen at preventing breast cancer from coming back. But it has
different side effects. Anastrozole generally has fewer side effects than tamoxifen,
although it is more likely to cause weakening of the bones (osteoporosis). The
weakening can lead to joint pain or bone fractures. A rare side effect of anastrozole is
an increase in the amount of cholesterol in the blood which can lead to heart
problems.
A trial called the Intergroup Exemestane Study (IES trial) compared tamoxifen for 2
to 3 years followed by exemestane (Aromasin), with tamoxifen only for 5 years. The
results showed that switching to exemestane lowered the risk of the cancer coming
back more than staying on tamoxifen.
Another aromatase inhibitor called letrozole (Femara), has been tested and licensed
for early breast cancer. You may also have letrozole before surgery to try to shrink
your cancer so that you can have a smaller operation to remove it.1
Aromatase inhibitors to prevent breast cancer
A major trial looked at anastrozole as a way of preventing breast cancer in women at
high risk of the disease. This trial is called IBIS 2 and showed that anastrozole can
reduce the risk of developing breast cancer by 50% in women at high risk. You can
find detailed information about the IBIS 2 trialon our clinical trials database.
1.3 How is hormone therapy used to treat breast cancer?
There are three main ways that hormone therapy is used to treat hormone-sensitive
breast cancer:2
1.Adjuvant therapy for early-stage breast cancer: Research has shown that
women treated for early-stage ER-positive breast cancer benefit from receiving at
least 5 years of adjuvant hormone therapy. Adjuvant therapy is treatment given after

the main treatment (surgery, in the case of early-stage breast cancer) to increase the
likelihood of a cure.
Adjuvant therapy may include radiation therapy and some combination
of chemotherapy, hormone therapy, and targeted therapy. Tamoxifen has been
approved by the FDA for adjuvant hormone treatment of premenopausal and
postmenopausal women (and men) with ER-positive early-stage breast cancer,
and anastrozole and letrozole have been approved for this use in postmenopausal
women.
A third aromatase inhibitor, exemestane, is approved for adjuvant treatment of earlystage breast cancer in postmenopausal women who have received tamoxifen
previously.
Until recently, most women who received adjuvant hormone therapy to reduce the
chance of a breast cancer recurrence took tamoxifen every day for 5 years. However,
with the advent of newer hormone therapies, some of which have been compared
with tamoxifen in clinical trials, additional approaches to hormone therapy have
become common . For example, some women may take an aromatase inhibitor every
day for 5 years, instead of tamoxifen. Other women may receive additional treatment
with an aromatase inhibitor after 5 years of tamoxifen. Finally, some women may
switch to an aromatase inhibitor after 2 or 3 years of tamoxifen, for a total of 5 or
more years of hormone therapy.2
Decisions about the type and duration of adjuvant hormone therapy must be made on
an individual basis. This complicated decision-making process is best carried out by
talking with an oncologist, a doctor who specializes in cancer treatment.
Treatment of metastatic breast cancer: Several types of hormone therapy are
approved to treat hormone-sensitive breast cancer that is metastatic (has spread to
other parts of the body).

Studies have shown that tamoxifen is effective in treating women and men with
metastatic breast cancer . Toremifene is also approved for this use. The
antiestrogen fulvestrantcan be used in postmenopausal women with metastatic ERpositive breast cancer after treatment with other antiestrogens .2
The aromatase inhibitors anastrozole and letrozole can be given to postmenopausal
women as initial therapy for metastatic hormone-sensitive breast cancer . These two
drugs, as well as the aromatase inhibitor exemestane, can also be used to treat
postmenopausal women with advanced breast cancer whose disease has worsened
after treatment with tamoxifen .
2.Neoadjuvant treatment of breast cancer: The use of hormone therapy to treat
breast cancer before surgery (neoadjuvant therapy) has been studied in clinical trials .
The goal of neoadjuvant therapy is to reduce the size of a breast tumor to
allow breast-conserving surgery. Data from randomized controlled trials have shown
that neoadjuvant hormone therapiesin particular, aromatase inhibitorscan be
effective in reducing the size of breast tumors in postmenopausal women. The results
in premenopausal women are less clear because only a few small trials involving
relatively few premenopausal women have been conducted thus far.2
1.3 Side Effects Of Hormone Therapy
The side effects of hormone therapy depend largely on the specific drug or the type
of treatment . The benefits and risks of taking hormone therapy should be carefully
weighed for each woman.
Hot flashes, night sweats, and vaginal dryness are common side effects of hormone
therapy. Hormone therapy also disrupts the menstrual cycle in premenopausal
women.
Less common but serious side effects of hormone therapy drugs are listed below.

Tamoxifen

Risk of blood clots, especially in the lungs and legs

Stroke

Cataracts

Endometrial and uterine cancers

Bone loss in premenopausal women

Mood swings, depression, and loss of libido

In men: headaches, nausea, vomiting, skin rash, impotence, and decreased

sexual interest

Raloxifene

Risk of blood clots, especially in the lungs and legs

Stroke in certain subgroups

Ovarian suppression

Bone loss

Mood swings, depression, and loss of libido

Aromatase inhibitors

Risk of heart attack, angina, heart failure, and hypercholesterolemia

Bone loss

Joint pain

Mood swings and depression

Fulvestrant

Gastrointestinal symptoms

Loss of strength

Pain

A common switching strategy, in which patients take tamoxifen for 2 or 3 years,

followed by an aromatase inhibitor for 2 or 3 years, may yield the best balance of
benefits and harms of these two types of hormone therapy 2
2.TARGET THERAPY
Targeted Therapy
In patients whose cancer expresses an over-abundance of the HER2 protein,
a monoclonal antibody known astrastuzumab (Herceptin) is used to block the activity
of the HER2 protein in breast cancer cells, slowing their growth. In the advanced
cancer setting, trastuzumab use in combination with chemotherapy can both delay
cancer growth as well as improve the recipient's survival. More recently, several
clinical trials have also confirmed that in the adjuvant setting, i.e. postoperative
following breast cancer surgery, the use of trastuzumab for up to one year also delays
the recurrence of breast cancer and improves survival.
Other types of targeted therapies that are being researched to fight cancer include:

Angiogenesis inhibitors. These antibodies prevent the growth of new blood

vessels, cutting off the supply of oxygen and nutrients to cancer cells.

Signal transduction inhibitors. These antibodies block signals inside the cancer
cell that helps the cells divide, stopping the cancer from growing.

Antibodies/antagonists for other hormones/receptors such as androgen

receptors and prolactin receptors, which are present in a high proportion of breast
cancers.1
Target

ER

AR in ER+
cancers

AR in ERcancers

Drug

Anastrozole (Arimidex)

Letrozole (Femara)

Exemestane (Aromasin)

Fulvestrant (Faslodex)

testosterone, synthetic
androgens, progestins

bicalutamide

Type

Aromatase inhibitor

Efficacy Trial

[26][unreliable medical source?]

Other

androgen agonist

androgen receptor
antagonist

Phase II MBC
testing
underway[27]

Trastuzumab (Herceptin)
[28]

HER2 receptor
protein

PRLR

Pertuzumab

neratinib (HKI-272) in
Phase II[29][unreliable medical source?]

lapatinib (TykerB)[30]

cabergoline

NeuVax

Monoclonal
antibody

Kinase inhibitor
selectivedopamine D
2
and serotoninagonist
reducingprolactinlev
els
Vaccine

very good results

in pretreated MBC
in combination
with docetaxel[31]
NeuVax is a
HER2/neu

dHER2

MVF-HER-2

E1A (gene therapy)

Trastuzumab
emtansine(Herceptin+DM1)[33]

peptide-based Tcell
immunotherapy
aimed at
preventing disease
recurrence and
prolonging
survival in cancer
patients that have
tumors expressing
the HER2/neu
oncoprotein. To
date, clinical study
results have
demonstrated that
NeuVax
significantly
reduces the rate of
cancer recurrence
while showing
minimal side
effects[32]

Other

[unreliable medical source?]

HER1/ EGFR

Iressa (gefitinib)[34][unreliable
medical source?]

Cetuximab[35][unreliable medical
source?]

tyrosine kinase
inhibitor

However, clinical
studies did not find
most EGFR
inhibitors effective
against breast
cancer for a large
enough proportion
of patients. Some
oncologists believe
it may be possible
to select a fraction
of patients, either

through genetics or
the characteristics
of their tumors,
who have a better
chance of having
the drugs work[36]
[unreliable medical source?]

insulin-like
growth factor-1
receptor (IGF1R)

insulin-like
growth factor-1
receptor (IGF1R) and insulin
receptor (IR)

PI3K/AKT/mT
OR cell survival
pathway

VEGF receptor
protein
(involved
in forming
tumor blood
vessels)

IMC-A12[37][unreliable medical
source?]

CP-751, CP-871

AMG 479

h7C10

Linsitinib (OSI-906)

BGT226

BEZ235A

RAD001

Rapamycin

Bevacizumab (Avastin)

ramucirumab

Sunitinib

Monoclonal
antibody

Dual kinase
inhibitor

Kinase inhibitor

Monoclonal
antibody

Kinase inhibitor

AVADO[37][unreliable
medical source?]

P53

PARP protein
inhibitor

Vatalinib

Pazopanib

AZD2171

AMG706

AMG386

PTC299

P53 peptide vaccine

Gendicine (from China)

d5CMV-p53 (INGN 201)

ALT801 (p53 inhibitor)

Anti-p53 T-cell reinfusion

AFP-464 (phase I for triple

-ve)[38][unreliable medical source?]

Olaparib (Phase I with

good results)

Other

Vaccine

Gene therapy

Other

DNA repair blocker

- kills cancer cells
with a faulty
BRCA1 or BRCA2
Iniparib (Phase II excellent
gene by preventing
results)[39][unreliable medical source?]
the repair of DNA.
A cell with a BRCA
BSI-201 (Phase II fault relies on a
Clinical Benefit in 62% Of
protein
Patients With Triple-Negative)
called PARPto keep
its DNA healthy.
veliparib
Olaparib, known as
a 'PARP-inhibitor',
blocks PARP, which
causes the cancer
cells to die.

Olaparib - In the
initial findings,
Over 40% of
tumours in the
higher dose group
reduced
significantly in
size, and tumours
were prevented
from progressing
for an average of
six months, while
one patient's
tumour
disappeared

completely in a
heavily pre-treated
set of patiens in an
ongoning trail.[40]
[unreliable medical source?]

BSI-201 - Among
other
investigational
PARP inhibitors in
the industry, BSI201 is the furthest
along in clinical
development in
metastatic TNBC.
BSI-201 is
currently being
evaluated for its
potential to
enhance the effect
of chemotherapyinduced DNA
damage. The
clinical
development of
BSI-201 is
supported by well
documented safety
profile based on
studies of more
than 200 patients.
[41][unreliable medical source?]

ATGR1 (ERBB
2)

Losartan (blood pressure

drug)

AGTR1 is seen in
10 percent to 20
percent of breast
tumors. Specifically,
overexpressed only
in tumors that are
HER2-negative and

[42][unreliable medical source?]

ER-positive.
AGTR1 was found
to be as much as
100-fold
overexpressed in
some tumors.

eIF4E gene

ribavirin (a common antiviral drug)

eIF4E gene is
dysregulated in 30
percent of cancers
including breast,
prostate, head and
neck, colon and
stomach cancer.

The trial studied

patients with
M4/M5acute
myeloid
leukemia who had
undergone several
other treatments
that had previously
failed. They had
striking clinical
improvements
with even partial
and complete
remissions.[43]
[unreliable medical source?]

Other Targets

Dasatinib (SRC inhibitor)

Kinase inhibitor

Drug already used

to treat CML is a
possible cure for a
subset of breast
cancer population
who test positive
for alpha-v beta-3.
[44][unreliable medical source?]

Saracatinib (SRC
inhibitor)

Kinase inhibitor

Combining
Herceptin and
saracatinib to treat
resistant tumors in
mice reduced
tumor volume by
90 percent in 25
days. Herceptin
alone kept tumor

volume about the

same during the
same period, while
control and
saracatinib alone
permitted growth
of more than 200
percent.[45][unreliable
medical source?]

Sorafenib(Nexavar)[46]
[unreliable medical source?]

AS1402 anti-MUC1
antibody[47][unreliable medical source?]

THERATOPE

Dendritic cell vaccines

C1311 in phase II
(topoisomerase II inhibitor)

multi-kinase
inhibitor

Vaccine -Stimuvax

Other

Bavituximab in Phase II[48]

[unreliable medical source?]

TABLE 1:TARGET THERAPY DRUGS

2.1 NEW ADVANCES

Targeted therapies
Targeted therapies are a group of newer drugs that specifically take advantage of
gene changes in cells that cause cancer.1

Drugs that target HER2: A number of drugs that target HER2 are currently in use,
including trastuzumab (Herceptin), pertuzumab (Perjeta), ado-trastuzumab emtansine
(Kadcyla), and lapatinib (Tykerb). Other drugs are being developed and tested.
Anti-angiogenesis drugs: For cancers to grow, blood vessels must develop to
nourish the cancer cells. This process is called angiogenesis. Looking at angiogenesis
in breast cancer specimens can help predict prognosis. Some studies have found that
breast cancers surrounded by many new, small blood vessels are likely to be more
aggressive. More research is needed to confirm this.
Bevacizumab (Avastin) is an example of anti-angiogenesis drug. Although
bevacizumab turned out to not be very helpful in the treatment of advanced breast
cancer, this approach still may prove useful in breast cancer treatment. Several other
anti-angiogenesis drugs are being tested in clinical trials.1
Other targeted drugs: Everolimus (Afinitor) is a targeted therapy drug that seems to
help hormone therapy drugs work better. It is approved to be given with exemestane
(Aromasin) to treat advanced hormone receptor-positive breast cancer in postmenopausal women. It has also been studied with other hormone therapy drugs and
for treatment of earlier stage breast cancer. In one study, letrozole plus everolimus
worked better than letrozole alone in shrinking breast tumors before surgery. It also
seemed to help in treating advanced hormone receptor-positive breast cancer when
added to tamoxifen. Everolimus is also being studied in combination with
chemotherapy and the targeted drug trastuzumab. Other drugs like everolimus are
also being studied.
Other potential targets for new breast cancer drugs have been identified in recent
years. Drugs based on these targets are now being studied, but most are still in the
early stages of clinical trials.
Bisphosphonates

Bisphosphonates are drugs that are used to help strengthen and reduce the risk of
fractures in bones that have been weakened by metastatic breast cancer. Examples
include pamidronate (Aredia) and zoledronic acid (Zometa).
Some studies have suggested that zoledronic acid may help other systemic therapies,
like hormone treatment and chemo work better. In one study of women being treated
with chemo before surgery, tumors in the women getting zoledronic acid with chemo
shrank more than those in the women treated with chemo alone.
Other studies have looked at the effect of giving zoledronic acid with other adjuvant
treatments (like chemo or hormone therapy). So far, the results have been mixed.
Some studies have shown that this approach helped lower the risk of the cancer
coming back, but others did not. The results of one study linked the use of these
drugs with adjuvant chemo with an increased risk of breast cancer recurrence in
younger women. Overall, the data does not support making bisphosphonates part of
standard therapy for early-stage breast cancer.
Denosumab
Denosumab (Xgeva, Prolia) can also be used to help strengthen and reduce the risk of
fractures in bones that have been weakened by metastatic breast cancer. It is being
studied to see if it can help adjuvant treatments work better.1
Vitamin D
A recent study found that women with early-stage breast cancer who were vitamin D
deficient were more likely to have their cancer recur in a distant part of the body and
had a poorer outlook. More research is needed to confirm this finding. It is not yet
clear if taking vitamin D supplements would be helpful. Still, you might want to talk
to your doctor about testing your vitamin D level to see if it is in the healthy range.
3.ENDOCRINE THERAPY

Endocrine Therapy
Women who have been diagnosed with estrogen receptor-positive breast cancer will
often be prescribed daily oral medication after all other treatment ends. Endocrine
therapy is prescribed differently for women, depending on whether they are
premenopausal or postmenopausal.1

Endocrine Therapy for Premenopausal Women

Premenopausal women with breast cancers that express the estrogen and/or
progesterone receptor (ER and/or PR-positive) will often be encouraged to
take tamoxifen for five years. This drug impacts the effects of estrogen in cancer cells
and helps reduce the risk that the breast cancer will recur in women of any age by
almost 50 percent.
Tamoxifen can also help reduce the risk of developing a new breast cancer in the
unaffected breast. In some cases, women who are younger than 35-40 may also be
considered for combined endocrine therapy with medications that temporarily stop
ovarian function.2
NOTE: Many women stop menstruating after receiving chemotherapy, often for
several months or even a few years. It is possible that these women could still have
functioning ovaries and premenopausal hormonal levels despite the absence of their
menstrual periods. Also, ovarian function could still return unexpectedly. That said,
women who are premenopausal, regardless of whether they experience temporary
menopause because of treatments, should not be prescribed aromatase inhibitors
(unless they are participating in specific clinical research studies). Aromatase
inhibitors are typically reserved for postmenopausal women with breast cancer.
Side effects of tamoxifen

The side effects of tamoxifen are generally mild and decrease with time. They
include:

Hot flashes

Vaginal discharge

Menstrual irregularity

Hair loss

Skin changes

Decreased interest in sexual activity

Fertility issues

Memory loss

Fatigue

Joint pain

Headaches

Insomnia or trouble sleeping

Increased sweating

Nausea

Weight changes

Mood swings
Some side effects can be alleviated through symptom management and other lifestyle
changes.
Risk Factors

Serious complications with tamoxifen are rare, especially in women younger than age
50, and may include blood clots (deep venous thrombosis or pulmonary embolism) or
uterine (endometrial) cancer.2
Ovarian Suppression or Ablation
For premenopausal women with estrogen receptor-positive breast tumors, ovarian
ablation or suppression (stopping ovary function) may be an option. Since a
premenopausal womans ovaries are the main source of estrogen production,
temporarily or permanently shutting off their function has been shown to be effective
(when used alone) in reducing the chances of a breast cancer recurrence. Studies are
now confirming their usefulness when given with tamoxifen instead of chemotherapy
or after chemotherapy. This is called ovarian ablation or suppression and can be done
through surgery (permanently) or monthly hormonal injections (temporarily). The
injection of medication will prevent you from ovulating or menstruating and will put
you in temporary menopause. Surgery will prevent you from having to undergo
monthly injections, but will put you in irreversible menopause. 2
Ovarian Ablation
A bilateral oophorectomy (or ovarian ablation) is the surgical removal of your
ovaries. This procedure is sometimes recommended if you have been identified as
carrying a BRCA1 or BRCA2 genetic mutation and have an increased risk of
developing ovarian cancer. The surgical removal of your ovaries will reduce
circulating estrogens in your body down to postmenopausal levels. This surgery is
permanent and cannot be undone. For premenopausal women, an oophorectomy will
prevent you from conceiving children and will cause permanent menopause.
Ovarian Suppression

Ovary suppression can be achieved by hormonal drug injections called gonadotropinreleasing hormone (LH-RH or GnRH) agonist. This works by temporarily
suppressing ovulation and, as a result, limiting the amount of estrogen circulating in
your body. Estrogen levels usually are reduced to postmenopausal levels within two
weeks. Treatment is generally administered by monthly injections. Although you will
be in a temporary menopause while taking this drug, this is generally reversible and
menstruation often begins shortly after treatment stops. This is not a fail-proof birth
control method so you should use a non-hormonal form of contraception too, like an
IUD or barrier methods such as condoms or a diaphragm. Side effects are similar to
menopausal symptoms and include decreased sex drive, hot flashes, weight gain and
bone pain.3
To maximize effectiveness, ovarian suppression drugs and tamoxifen are prescribed
together.
Drug interactions
Antidepressants
It is estimated that as many as 30 percent of all breast cancer patients in the United
States are prescribed an antidepressant at sometime during their treatment. Some
antidepressants interfere with how tamoxifen works and therefore should be avoided.
The following antidepressants are expected to interfere with tamoxifen:
Paxil (paroxetine)
Prozac (fluoxetine)
Wellbutrin (bupropion)
The following drugs are believed to have a moderate interference with tamoxifen:

Zoloft(sertraline)
Cymbalta (duloxetine)
The following antidepressants have been shown to be less likely or unlikely to
interfere with tamoxifen:
Effexor (venlafaxine)
Lexapro (escitalopram)
Celexa(citalopram)
Other Medications
There are other drugs that are not classified as antidepressants but are believed to
interfere with tamoxifen and should be avoided. These include:
Cardioquin (quinidine)
Benadryl (diphenhydramine)
Mellaril (thioridazine)
Cordarone(amiodarone)
Tagamet (cimetidine)
NOTE: Many women stop menstruating after receiving chemotherapy, often for
several months or even a few years. This does not necessarily mean they are
postmenopausal. It is possible that these women could still have functioning ovaries
and premenopausal hormonal levels despite the absence of their menstrual periods.
Also, ovarian function could still return unexpectedly. That said, women who are
premenopausal, regardless of whether they experience temporary menopause because
of treatments, should not be prescribed aromatase inhibitors (unless they are
participating in specific clinical research studies). Aromatase inhibitors are typically
reserved for postmenopausal women with breast cancer.3
Complications

Bone loss can be a complication of aromatase inhibitors. All women who have started
or will start an aromatase inhibitor should talk to their primary care provider about
having a bone density study (DEXA scan). Patients also should take at least the
minimum recommended daily allowances of calcium and vitamin D. In patients with
some evidence of bone loss, your doctor may recommend that you increase your
exercise level or take a calcium supplement. If you are still experiencing problems
with bone loss, your doctor may prescribe bone building drugs like a class of
medications called bisphosphonates. The drug Evista (raloxifene) is quite similar to
tamoxifen and in general should be avoided in women previously diagnosed with
breast cancer.3
4.BONE DETECTION THERAPY
Bone-directed therapy for breast cancer
When cancer spreads to bones, it can cause pain and lead to bones breaking
(fractures) and other problems. Drugs like bisphosphonates and denosumab can
lower the risk of these problems.2
BISPHOSPHONATES
Bisphosphonates are drugs that can be used to help strengthen bones and reduce the
risk of fractures and pain in bones that have been weakened by metastatic breast
cancer. Examples include pamidronate (Aredia) and zoledronic acid (Zometa). They
are given intravenously (IV).
Bisphosphonates may also help against bone thinning (osteoporosis) that can result
from treatment with aromatase inhibitors or from early menopause as a side effect of
chemotherapy. There are a number of medicines, including some oral forms of
bisphosphonates, to treat loss of bone strength when it is not caused by cancer spread
to the bones.

Bisphosphonates can have side effects, including flu-like symptoms and bone pain.
They can also lead to kidney problems, so people with poor kidney function may not
be able to be treated with these drugs.
A rare but very distressing side effect of bisphosphonates is osteonecrosis (damage)
in the jaw bones or ONJ. It can be triggered by having a tooth removed while getting
treated with a bisphosphonate. ONJ often appears as an open sore in the jaw that
won't heal. It can lead to loss of teeth or infections of the jaw bone. Doctors don't
know why this happens or how to treat it, other than to stop the bisphosphonates.
Maintaining good oral hygiene by flossing, brushing, making sure that dentures fit
properly, and having regular dental checkups may help prevent this. Most doctors
recommend that you have a dental checkup and have any tooth or jaw problems
treated before starting bisphosphonate treatment.
Denosumab
Denosumab (Xgeva, Prolia) is another drug that can help reduce the risk of problems
from breast cancer metastasis to the bone. It works differently from bisphosphonates.
In studies of patients with breast cancer that had spread to the bone, it seemed to help
prevent problems like fractures (breaks) better than zoledronic acid. It also can help
bones even after bisphosphonates stop working.
In patients with cancer spread to bones, this drug is injected under the skin every 4
weeks. Side effects include low blood levels of calcium and phosphate, as well as
ONJ This drug does not seem to affect the kidneys, so it is safe to take if you have
kidney problems.
Denosumab can also be used to strengthen bones in breast cancer patients with weak
bones who are being treated with aromatase inhibitors. When it is used for this
purpose, it is given less often (usually every 6 months).

5.CHEMO THERAPY
5.1Chemotherapy for breast cancer
Chemotherapy (chemo) is treatment with cancer-killing drugs that may be given
intravenously (injected into a vein) or by mouth. The drugs travel through the
bloodstream to reach cancer cells in most parts of the body. Chemo is given in cycles,
with each period of treatment followed by a recovery period. Treatment usually lasts
for several months.3
5.2.When is chemotherapy used.
There are several situations in which chemo may be recommended.
After surgery (adjuvant chemotherapy): When therapy is given to patients with no
evidence of cancer after surgery, it is called adjuvant therapy. Surgery is used to
remove all of the cancer that can be seen, but adjuvant therapy is used to kill any
cancer cells that may have been left behind or spread but can't be seen, even on
imaging tests. If these cells are allowed to grow, they can establish new tumors in
other places in the body. Adjuvant therapy after breast-conserving surgery or
mastectomy reduces the risk of breast cancer coming back. Radiation,
chemo, targeted therapy, and hormone therapy can all be used as adjuvant treatments.
Before surgery (neoadjuvant chemotherapy): Neoadjuvant therapy is like adjuvant
therapy, except you get the treatments (or at least start them) before surgery instead
of after. In terms of survival and the cancer coming back, there is no difference
between getting chemo before or after surgery. But neoadjuvant chemo does have
two benefits. First, chemo may shrink the tumor so that it can be removed with less
extensive surgery. That is why neoadjuvant chemo is often used to treat cancers that
are too big to be surgically removed at the time of diagnosis (called locally
advanced). Also, by giving chemo before the tumor is removed, doctors can better

see how the cancer responds. If the first set of drugs do not shrink the tumor, your
doctor will know that other drugs are needed.1
For advanced breast cancer: Chemo can also be used as the main treatment for
women whose cancer has spread outside the breast and underarm area, either when it
is diagnosed or after initial treatments. The length of treatment depends on whether
the cancer shrinks, how much it shrinks, and how well you tolerate treatment.
5.3.How Chemotherapy Given?
In most cases (especially adjuvant and neoadjuvant treatment), chemo is most
effective when combinations of more than one drug are used. Many combinations are
being used, and it's not clear that any single combination is clearly the best. The
most common chemo drugs used for early breast cancer include the anthracyclines
(such as doxorubicin/Adriamycin and epirubicin/Ellence) and the taxanes (such as
paclitaxel/Taxol and docetaxel/Taxotere). These may be used in combination with
certain other drugs, like fluorouracil (5-FU), cyclophosphamide (Cytoxan), and
carboplatin.
For cancers that are HER2 positive, the targeted drug trastuzumab (Herceptin) is
often given with one of the taxanes. Pertuzumab (Perjeta) can also be combined with
trastuzumab and docetaxel for HER2 positive cancers. 2
Many chemo drugs are useful in treating women with advanced breast cancer, such
as:

Docetaxel

Paclitaxel

Platinum agents (cisplatin, carboplatin)

Vinorelbine (Navelbine)

Capecitabine (Xeloda)

Liposomal doxorubicin (Doxil)

Gemcitabine (Gemzar)

Mitoxantrone

Ixabepilone (Ixempra)

Albumin-bound paclitaxel (nab-paclitaxel or Abraxane)

Eribulin (Halaven)

Although drug combinations are often used to treat early breast cancer, advanced
disease is more often treated with single chemo drugs. Still some combinations, such
as carboplatin or cisplatin plus gemcitabine are commonly used to treat advanced
breast cancer.
One or more drugs that target HER2 may be used with chemo for tumors that are
HER2-positive
Doctors give chemo in cycles, with each period of treatment followed by a rest
period to give the body time to recover from the effects of the drugs. Chemo begins
on the first day of each cycle, but the schedule varies depending on the drugs used.
For example, with some drugs, the chemo is given only on the first day of the cycle.
With others, it is given every day for 14 days, or weekly for 2 weeks. Then, at the end
of the cycle, the chemo schedule repeats to start the next cycle. Cycles are most often
2 or 3 weeks long, but they vary according to the specific drug or combination of
drugs. Some drugs are given more often. Adjuvant and neoadjuvant chemo is often
given for a total of 3 to 6 months, depending on the drugs that are used. Treatment
may be longer for advanced breast cancer and is based on how well it is working and
what side effects you have.1
Dose-dense chemotherapy: Doctors have found that giving the cycles of certain
chemo agents closer together can lower the chance that the cancer will come back
and improve survival in some women. This usually means giving the same chemo

that may be given every 3 weeks (such as AC T), but giving it every 2 weeks. A
drug (growth factor) to help boost the white blood cell count is given after chemo to
make sure the white blood cell count returns to normal in time for the next cycle.
This approach can be used for neoadjuvant and adjuvant treatment. It can lead to
more problems with low blood cell counts, so it isnt for everyone.2
5.4.Possible side effects
Chemo drugs work by attacking cells that are dividing quickly, which is why they
work against cancer cells. But other cells in the body, like those in the bone marrow,
the lining of the mouth and intestines, and the hair follicles, also divide quickly.
These cells are also likely to be affected by chemo, which can lead to side effects.
Some women have many side effects; others may only have few.
Chemo side effects depend on the type of drugs, the amount taken, and the length of
treatment. Some of the most common possible side effects include:

Hair loss and nail changes

Mouth sores

Loss of appetite or increased appetite

Nausea and vomiting

Low blood cell counts

Chemo can affect the blood forming cells of the bone marrow, which can lead to:

Increased chance of infections (from low white blood cell counts)

Easy bruising or bleeding (from low blood platelet counts)

Fatigue (from low red blood cell counts and other reasons)

These side effects usually last a short time and go away after treatment is finished.
It's important to tell your health care team if you have any side effects, as there are
often ways to lessen them. For example, drugs can be given to help prevent or reduce
nausea and vomiting.
Other side effects are also possible. Some of these are more common with certain
chemo drugs. Your cancer care team will tell you about the possible side effects of
the specific drugs you are getting.1
Menstrual changes: For younger women, changes in menstrual periods are a
common side effect of chemo. Premature menopause (not having any more menstrual
periods) and infertility (not being able to become pregnant) may occur and may be
permanent. Some chemo drugs are more likely to cause this than others. The older a
woman is when she receives chemotherapy, the more likely it is that she will become
infertile or go through menopause as a result. When this happens, there is an
increased risk of bone loss and osteoporosis. There are medicines that can treat or
help prevent problems with bone loss.
Even if your periods have stopped while you were on chemo, you may still be able to
get pregnant. Getting pregnant while receiving chemo could lead to birth defects and
interfere with treatment. If you are pre-menopausal before treatment and are sexually
active, it is important to discuss using birth control with your doctor. For women with
hormone receptor-positive breast cancer, some types of hormonal birth control (like
birth control pills) are not good idea, so it is important to talk with both your
oncologist and your gynecologist (or family doctor) about what options would be
best in your case. Women who have finished treatment (like chemo) can safely go on
to have children, but it's not safe to get pregnant while on treatment.
Neuropathy: Many drugs used to treat breast cancer, including the taxanes
(docetaxel and paclitaxel), platinum agents (carboplatin, cisplatin), vinorelbine,

erubulin, and ixabepilone, can damage nerves outside of the brain and spinal cord.
This can sometimes lead to symptoms (mainly in the hands and feet) like numbness,
pain, burning or tingling sensations, sensitivity to cold or heat, or weakness. In most
cases this goes away once treatment is stopped, but it might last a long time in some
women.1
Heart damage: Doxorubicin, epirubicin, and some other drugs may cause permanent
heart damage (calledcardiomyopathy). The risk of this occurring depends on how
much of the drug is given, and is highest if the drug is used for a long time or in high
doses. Doctors watch closely for this side effect. Most doctors will check your heart
function with a test like a MUGA or an echocardiogram before starting one of these
drugs. They also carefully control the doses, watch for symptoms of heart problems,
and may repeat the heart test to monitor function. If the heart function begins to
decline, treatment with these drugs will be stopped. Still, in some people, heart
damage takes a long time to develop. Signs might not appear until months or years
after treatment stops. Heart damage from these drugs happens more often if other
drugs that can cause heart damage, such as trastuzumab and other drugs that target
HER2 are used as well, so doctors are more cautious when these drugs are used
together.2
Hand-foot syndrome: Certain chemo drugs, such as capecitabine and liposomal
doxorubicin, can irritate the palms of the hands and the soles of the feet. This is
called hand-foot syndrome. Early symptoms include numbness, tingling, and redness.
If it gets worse, the hands and feet can become swollen and uncomfortable or even
painful. The skin may blister, leading to peeling of the skin or even open sores. There
is no specific treatment, although some creams may help. These symptoms gradually
get better when the drug is stopped or the dose is decreased. The best way to prevent
severe hand-foot syndrome is to tell your doctor when early symptoms come up, so
that the drug dose can be changed. This syndrome can also occur when the drug 5-FU
is given as an IV infusion over several 2

Chemo brain: Another possible side effect of chemo is "chemo brain." Many
women who are treated for breast cancer report a slight decrease in mental
functioning. They may have some problems with concentration and memory, which
may last a long time. Although many women have linked this to chemo, it also has
been seen in women who did not get chemo as a part of their treatment. Still, most
women function well after treatment. In studies that have found chemo brain to be a
side effect of treatment, the symptoms most often go away in a few years.
Increased risk of leukemia: Very rarely, certain chemo drugs can permanently
damage the bone marrow, leading to a disease called myelodysplastic syndrome or
even acute myeloid leukemia, a life-threatening cancer of white blood cells. When
this happens it is usually within 10 years after treatment. In most women, the benefits
of chemo in preventing breast cancer from coming back or in extending life are likely
to far exceed the risk of this rare but serious complication.2
Feeling unwell or tired: Many women do not feel as healthy after receiving chemo
as they did before. There is often a residual feeling of body pain or achiness and a
mild loss of physical functioning. These may be very subtle changes that are only
revealed by closely questioning women who have undergone chemo.
Fatigue is another common (but often overlooked) problem for women who have
received chemo. This may last up to several years. It can often be helped, so it is
important to let your doctor or nurse know about it. For more information on what
you can do about fatigue, see Fatigue in People with Cancer. Exercise, naps, and
conserving energy may be recommended. If you have sleep problems, they can be
treated. Sometimes there is depression, which may be helped by counseling and/or
medicines.
Chemotherapy uses medicine to kill cancer cells. With breast cancer, it has three
major purposes:

1.

To prevent cancer from coming back after surgery and radiation. When
chemotherapy is used this way, its called adjuvant therapy.

2.

To shrink a tumor before surgery to make it easier to remove. This is

called neo-adjuvant therapy.

3.

To kill cancer cells that have spread to other parts of the body.
Together, you and your doctor will decide when to start chemotherapy, what drugs to
use, and a schedule for taking them. Ask what side effects you may expect
from medication.2
Get Your Personalized Breast Cancer Treatment Report
Common Chemotherapy Drugs for Breast Cancer
Chemotherapy drugs used to treat early breast cancer include:

Anthracyclines: This class of drugs includes doxorubicin(Adriamycin)

and epirubicin (Ellence).

Taxanes: This class of drugs includes docetaxel (Taxotere)

andpaclitaxel (Taxol).
These drugs are often used with others like carboplatin,cyclophosphamide (Cytoxan),
and fluorouracil (5-FU).
Women who have the HER2 gene may be given ado-trastuzumab emtansine
(Kadcyla), lapatinib (Tykerb), pertuzumab (Perjeta), ortrastuzumab (Herceptin).
Drugs used to treat advanced breast cancer include:

Albumin-bound paclitaxel (nab-paclitaxel or Abraxane)

Capecitabine (Xeloda)

Eribulin (Halaven)

Gemcitabine (Gemzar)

Ixabepilone (Ixempra)

Liposomal doxorubicin (Doxil)

Mitoxantrone

Paclitaxel

Platinum (carboplatin, cisplatin)

Vinorelbine (Navelbine)

.
5.5ISSUES RELATED TO CHEMOTHERAPY
Chemotherapy will almost certainly affect how you feel about sex and intimacy. You
may not feel like being intimate at a time when youre dealing with treatment or you
may find intimacy helps you feel more normal during an uncertain time. Everyones
reaction will be different.
If youre pre-menopausal its important to use contraception even if your periods
become irregular or stop completely as it is still possible to become pregnant.
Chemotherapy drugs can harm a developing foetus in the first three months of
pregnancy.
An intrauterine device (IUD or coil) can be used as long as its not the type that
releases hormones. Its thought that chemotherapy drugs cant pass into vaginal fluids
or semen, but this cant be completely ruled out as chemotherapy drugs can pass into
the blood and some other body fluids.

For the first few days after chemotherapy, you may want to avoid unprotected
intercourse, oral sex, or any contact that involves the sharing of body fluids to ensure
that your partner is not exposed to the chemotherapy drugs. Most hospital specialists
will advise using barrier protection such as condoms for a few days after treatment.2
5.6 Complementary therapies
Many people find that complementary therapies can help them cope with the side
effects of chemotherapy, even though there may not necessarily be research evidence
to support this. There are many different types including acupuncture, relaxation,
visualisation, aromatherapy, reflexology, meditation and hypnotherapy.
Some therapies are available in NHS hospitals, so ask your specialist or breast care
nurse for details of what is available to you. If youre thinking of trying a
complementary therapy you should go to a recognised practitioner.
Diet and supplements
You may be able to eat normally throughout chemotherapy or your eating habits may
change because of the side effects of your treatment. Some people will find they lose
weight during treatment, others may gain weight.
Many people wonder if they should follow a specific diet during chemotherapy and
there are many conflicting theories about diet and breast cancer, which can be
confusing. Its important to make sure you eat and drink what you feel able to,
wherever possible trying to maintain a healthy, well-balanced diet.
Travel
Check with your specialist team before booking a holiday or traveling, particularly
abroad. Its sometimes possible to plan your treatment around your trip.

If you plan to go somewhere hot, take care not to stay in the sun for long periods as
your skin may be more sensitive to the sun when having chemotherapy.
Its a good idea to avoid the sun during the hottest part of the day (11am3pm), use a
high-factor suncream and keep covered with light clothing and a hat.
Getting travel insurance while having treatment for breast cancer isnt always
straightforward. For more information, see our breast cancer and travel insurance
information.
Macmillan Cancer Support has information on travel and cancer(link is external).
Vaccinations
You should not have any live vaccines while youre having chemotherapy as they
could be harmful. Measles, rubella (German measles), polio, BCG (tuberculosis) and
yellow fever are live vaccines. Its usually safe to have these vaccinations six months
after your treatment finishes. Talk to your GP or specialist before having any
vaccinations.1
Inactivate vaccines, such as the seasonal flu vaccine, are safe and usually
recommended for people starting or on chemotherapy to reduce their risk of getting
the flu.
Your immune system needs to be healthy in order to make the antibodies to the
vaccine that protects you from the flu. Therefore its best to have the vaccination at
least two weeks before your chemotherapy starts. If youre already receiving
chemotherapy then you will need to talk to your hospital specialist or breast care
nurse about the best time to have your flu jab2

6.RADIATION THERAPY
6.1Radiation therapy for breast cancer
Radiation therapy is treatment with high-energy rays or particles that destroy cancer
cells. Radiation to the breast is often given after breast-conserving surgery to help
lower the chance that the cancer will come back in the breast or nearby lymph nodes.
Radiation may also be recommended after mastectomy in patients either with a
cancer larger than 5 cm, or when cancer is found in the lymph nodes.
Radiation is also used to treat cancer that has spread to other areas, for example to the
bones or brain.
Radiation therapy can be given externally (external beam radiation) or internally
(brachytherapy).2
External beam radiation therapy
This is the most common type of radiation therapy for women with breast cancer.
The radiation is focused from a machine outside the body on the area affected by the
cancer.
The extent of radiation depends on whether mastectomy or breast-conserving surgery
(BCS) was done and whether or not lymph nodes are involved.
If mastectomy was done and no lymph nodes had cancer, radiation is targeted at the
chest wall and the places where any drains exited the body.
If BCS was done, most often the entire breast gets radiation, and an extra boost of
radiation is given to the area in the breast where the cancer was removed to prevent it
from coming back in that area. The boost is often given after the treatments to the
whole breast have ended. It uses the same machine, but the beams are aimed at the

place where the cancer was removed. Most women dont notice different side effects
from boost radiation than from whole breast radiation.
If cancer was found in the lymph nodes under the arm, radiation may be given to this
area as well. In some cases, the area treated may also include supraclavicular lymph
nodes (nodes above the collarbone) and internal mammary lymph nodes (nodes
beneath the breast bone in the center of the chest).1
When given after surgery, external radiation therapy is usually not started until the
tissues have been able to heal, often a month or longer. If chemotherapy is to be
given as well, radiation therapy is usually delayed until chemotherapy is complete.
Before your treatments start, the radiation team will take careful measurements to
determine the correct angles for aiming the radiation beams and the proper dose of
radiation. They will make some ink marks or small tattoos on your skin that they will
use later as a guide to focus the radiation on the right area.Lotions, powders,
deodorants, and antiperspirants can interfere with external beam radiation therapy, so
your health care team may tell you not to use them until treatments are complete.
External radiation therapy is much like getting an x-ray, but the radiation is more
intense. The procedure itself is painless. Each treatment lasts only a few minutes, but
the setup timegetting you into place for treatmentusually takes longer.
Breast radiation is most commonly given 5 days a week (Monday through Friday) for
about 5 to 6 weeks.
Some older women who have breast conserving surgery for early stage breast cancer
dont need radiation. 1
Accelerated breast irradiation: The standard approach of getting external
radiation for 5 days a week over many weeks can be inconvenient for many

women. Some doctors are now using other schedules, such as giving slightly
larger daily doses over only 3 weeks.
Giving radiation in larger doses using fewer treatments is known as hypofractionated
radiation therapy. This approach was studied in a large group of women who had
been treated with breast conserving surgery (BCS) and who did not have cancer
spread to underarm lymph nodes.
When compared with giving the radiation over 5 weeks, giving it over only 3 weeks
was just as good at keeping the cancer from coming back in the same breast over the
first 10 years after treatment. Newer approaches now being studied give radiation
over an even shorter period of time. In one approach, larger doses of radiation are
given each day, but the course of radiation is shortened to only 5 days. Intraoperative
radiation therapy (IORT) is another approach that gives a single large dose of
radiation in the operating room right after BCS (before the breast incision is closed).
IORT requires special equipment and is not widely available.1
3D-conformal radiotherapy: In this technique, the radiation is given with
special machines so that it is better aimed at the area where the tumor was.
This allows more of the healthy breast to be spared. Treatments are given twice
a day for 5 days. Because only part of the breast is treated, this is considered to
be a form of accelerated partial breast irradiation.
Other forms of accelerated partial breast irradiation are described below, under
Brachytherapy. It is hoped that these approaches may prove to be at least equal to
the current, standard breast irradiation, but few studies have compared these new
methods directly to standard radiation therapy. It is not known if all of the newer
methods will still be as good as standard radiation after many years, so many doctors
still consider them experimental. Women who are interested in these approaches may

want to ask their doctor about taking part in clinical trials of accelerated breast
irradiation now going on.1
Possible side effects of external radiation: The main short-term side effects
of external beam radiation therapy to the breast are swelling and heaviness in
the breast, skin changes in the treated area, and fatigue.
Skin changes can range from mild redness to blistering and peeling. Changes to the
breast tissue usually go away in 6 to 12 months, but it can take up to 2 years.
In some women, the breast becomes smaller and firmer after radiation therapy.
Women who have had breast radiation may have problems breastfeeding later on.
Radiation to the breast can also sometimes damage some of the nerves to the arm.
This is called brachial plexopathyand can lead to numbness, pain, and weakness in
the shoulder, arm and hand.
Radiation therapy of axillary lymph nodes also can cause lymphedema.
In rare cases, radiation therapy may weaken the ribs, which could lead to a fracture.
In the past, parts of the lungs and heart were more likely to get some radiation, which
could lead to long-term damage of these organs in some women. But modern
radiation therapy equipment allows doctors to better focus the radiation beams, so
these problems are rare today.
A very rare complication of radiation to the breast is the development of another
cancer called angiosarcoma. These rare cancers can grow and spread quickly.1
Brachytherapy
Brachytherapy, also known as internal radiation, is another way to deliver radiation
therapy. Instead of aiming radiation beams from outside the body, radioactive seeds

or pellets are placed into a device in the breast tissue in the area where the cancer had
been. It can be used along with external beam radiation in patients who had breast
conserving surgery (BCS) as a way to add an extra boost of radiation to the tumor
site. It may also be used by itself (instead of radiation to the whole breast). Tumor
size, location, and other factors may limit who can get brachytherapy.
There are different types of brachytherapy.1
Interstitial brachytherapy: In this approach, several small, hollow tubes
called catheters are inserted into the breast around the area where the cancer
was removed and are left in place for several days. Radioactive pellets are
inserted into the catheters for short periods of time each day and then removed.
This method of brachytherapy has been around longer (and has more evidence
to support it), but it is not used as much anymore.
Intracavitary brachytherapy: This is the most common type of
brachytherapy for women with breast cancer and is considered a form of
accelerated partial breast irradiation. A device is put into the space left from
BCS and is left in place until treatment is complete. There are several different
devices that can be used: MammoSit, SAVI, Axxent ,and Contura. They all go
into the breast as a small catheter (tube). The end of the device inside the
breast is then expanded so that it stays securely in the right place for the entire
treatment. The other end of the catheter sticks out of the breast.
For each treatment, one or more sources of radiation (often pellets) is placed down
through the tube and into the device for a short time and then removed. Treatments
are given twice a day for 5 days as an outpatient. After the last treatment, the device
is collapsed down again and removed.1

Early studies of intracavitary brachytherapy as the only radiation after breast

conserving surgery (BCS) had promising results, but didnt directly compare this
technique with standard whole breast external beam radiation.
One study that compared outcomes between intracavitary brachytherapy and whole
breast radiation after BCS found that women treated with brachytherapy were twice
as likely to go on to get a mastectomy of the treated breast (most likely because
cancer was found again in that breast). The overall risk was still low, however, with
about 4% of the women in the brachytherapy group needing mastectomy versus only
2% of the women in the whole breast radiation group.
This study raises questions about whether irradiating only the area around the cancer
will reduce the chances of the cancer coming back as much as giving radiation to the
whole breast. More studies comparing the 2 approaches are needed to see if
brachytherapy should be used instead of whole breast radiation.
Intracavitary brachytherapy can also have side effects, including redness, bruising,
breast pain, infection, and a break-down of an area of fat tissue in the breast. As with
whole breast radiation, weakness and fracture of the ribs can also occur.1
Radiation therapy schedule
Standard radiation therapy after a lumpectomy is external-beam radiation therapy
given Monday through Friday for 5 to 6 weeks. This often includes radiation therapy
to the whole breast the first 4 to 5 weeks, followed by a more focused treatment to
where the tumor was located in the breast for the remaining treatments.
This focused part of the treatment, called a boost, is standard for women with
invasive breast cancer to reduce the risk of a recurrence in the breast. Women with
DCIS may also receive the boost. For women with a low risk of recurrence, the boost
may be optional. It is important to discuss this treatment approach with your doctor.

If there is cancer in the lymph nodes under the arm, radiation therapy may also be
given to the same side of the neck or underarm near the breast or chest wall. Patients
who have a mastectomy may not need radiation therapy, depending on the features of
the tumor. Radiation may be recommended after mastectomy for a patient with a
larger tumor, for those with cancer in many lymph nodes, for those with cancer cells
outside of the capsule of the lymph node, and for those whose cancer has grown into
the skin or chest wall, as well as other reasons. Radiation therapy following a
mastectomy can be given after reconstruction, and is usually given 5 days a week for
5 to 6 weeks.
There has been growing interest in the use of newer regimens that shorten the length
of radiation treatment from 5 to 6 weeks to 3 to 4 weeks. In one method called hypofractionated radiation therapy, a higher daily dose is given to the whole breast so that
the overall length of treatment is shortened to 3 to 4 weeks. This approach can also be
combined with a boost to the tumor site either during or after the whole breast
radiation treatments. Even shorter schedules have been studied and are in use in some
centers, including accelerated partial breast radiation for 5 days, and others are
researching a 3-week schedule.1

7.BREAST RECONSTRUCTIVE SURGERIES

7.1Surgery
Surgery is the removal of the tumor and some surrounding healthy tissue during an
operation. Surgery is also used to examine the nearby underarm or axillary lymph
nodes. A surgical oncologist is a doctor who specializes in treating cancer with
surgery. Learn more about the basics of cancer surgery.3

Generally, the smaller the tumor, the more surgical options a patient has. The types of
surgery include the following:
A lumpectomy is the removal of the tumor and a small, cancer-free margin of
healthy tissue around the tumor. Most of the breast remains. For both DCIS
and invasive cancer, radiation therapy to the remaining breast tissue is
generally recommended after surgery. A lumpectomy may also be called
breast-conserving surgery, a partial mastectomy, quadrantectomy, or a
segmental mastectomy.
A mastectomy is the surgical removal of the entire breast. There are several
types of mastectomies. Talk with your doctor about whether the skin can be
preserved, called a skin-sparing mastectomy, or the nipple, called a total skinsparing mastectomy.3
Mastectomy
Mastectomy is the removal of the whole breast. There are five different types of
mastectomy: "simple" or "total" mastectomy, modified radical mastectomy, radical
mastectomy, partial mastectomy, and subcutaneous (nipple-sparing) mastectomy.
1 "Simple" or "total" mastectomy
Simple or total mastectomy concentrates on the breast tissue itself:
The surgeon removes the entire breast.
The surgeon does not perform axillary lymph node dissection (removal of
lymph nodes in the underarm area). Sometimes, however, lymph nodes are
occasionally removed because they happen to be located within the breast
tissue taken during surgery.

 No muscles are removed from beneath the breast.3

FIGURE 1:Simple Mastectomy

2 Modified radical mastectomy

Modified radical mastectomy involves the removal of both breast tissue and lymph
nodes:
The surgeon removes the entire breast.
Axillary lymph node dissection is performed, during which levels I and II of
underarm lymph nodes are removed (B and C in illustration).
No muscles are removed from beneath the breast.

FIGURE2:MODIFIED RADICAL MASTECTOMY

3 Radical mastectomy
Radical mastectomy is the most extensive type of mastectomy:
The surgeon removes the entire breast.
Levels I, II, and III of the underarm lymph nodes are removed (B, C, and D in
illustration).
The surgeon also removes the chest wall muscles under the breast.

FIGURE 3:RADICAL MASTECTOMY

4 Partial mastectomy

Partial mastectomy is the removal of the cancerous part of the breast tissue and some
normal tissue around it. While lumpectomy is technically a form of partial
mastectomy, more tissue is removed in partial mastectomy than in lumpectomy.3
5 Subcutaneous ("nipple-sparing") mastectomy
During subcutaneous ("nipple-sparing") mastectomy, all of the breast tissue is
removed, but the nipple is left alone. Subcutaneous mastectomy is performed less
often than simple or total mastectomy because more breast tissue is left behind
afterwards that could later develop cancer. Some physicians have also reported that
breast reconstruction after subcutaneous mastectomy can result in distortion and
possibly numbness of the nipple. Because subcutaneous mastectomy is still an area of
controversy among some physicians, your doctor may recommend simple or total
mastectomy instead.
Complications of Breast Cancer Surgery
Breast cancer surgery is generally considered safe, but as with any surgery, there are
risks.
Possible problems include:
Infection.
Hematoma.A build-up of blood under your skin
Seroma. A build-up of fluid under your skin
Lymphedema. Swelling in the arm
A bad reaction to anesthesia3

7.2Lymph node removal and analysis

Cancer cells can be found in the axillary lymph nodes in some cancers. It is important
to find out whether any of the lymph nodes near the breast contain cancer. This
information is used to determine treatment and prognosis.33
Sentinel lymph node biopsy. The sentinel lymph node biopsy procedure
allows for the removal of one to a few lymph nodes, avoiding the removal of
multiple lymph nodes in an axillary lymph node dissection (see below)
procedure for patients whose sentinel lymph nodes are free of cancer. The
smaller lymph node procedure helps lower the risk of several possible side
effects, including swelling of the arm called lymphedema, the risk of
numbness, as well as arm movement and range-of-motion problems, which are
long-lasting issues that can severely affect a persons quality of life.
In a sentinel lymph node biopsy, the surgeon finds and removes about one to
three sentinel lymph nodes from under the arm that receive lymph drainage
from the breast. The pathologist then examines these lymph nodes for cancer
cells. To find the sentinel lymph node, the surgeon injects a dye and/or a
radioactive tracer into the area of the cancer and/or around the nipple. The dye
or tracer travels to the lymph nodes, arriving at the sentinel node first. The
surgeon can find the node when it turns color if the dye is used or gives off
radiation if the tracer is used.
Axillary lymph node dissection. In an axillary lymph node dissection, the
surgeon removes many lymph nodes from under the arm, which are then
examined by a pathologist for cancer cells. The actual number of lymph nodes
removed varies from person to person. Recent research has shown that an
axillary lymph node dissection may not be needed for all women with earlystage breast cancer with small amounts of cancer in the sentinel lymph nodes.

Women having a lumpectomy and radiation therapy who have a smaller tumor
and no more than two sentinel lymph nodes containing cancer may avoid a full
axillary lymph node dissection, which helps reduce the risk of side effects and
does not decrease survival. If cancer is found in the sentinel lymph node,
whether more surgery is needed to remove additional lymph nodes varies
depending on the specific situation.3
7.3Reconstructive (plastic) surgery
Women who have a mastectomy may want to consider breast reconstruction, which is
surgery to create a breast form using either tissue taken from another part of the body
or synthetic implants. Reconstruction is usually performed by a plastic surgeon. A
woman may be able to have reconstruction at the same time as the mastectomy,
called immediate reconstruction, or at some point in the future, called delayed
reconstruction. In addition, reconstruction may be done at the same time as a
lumpectomy to improve the look of the breast and to match the breasts. This is called
oncoplastic surgery, and many breast surgeons can do this without the help of a
plastic surgeon. Surgery on the healthy breast is also often done so both breasts have
a similar appearance.3
The techniques discussed below are typically used to shape a new breast.
Implants.A breast implant uses saline-filled or silicone gel-filled forms to
reshape the breast. The outside of a saline-filled implant is made up of silicone,
and it is filled with sterile saline, which is salt water. Silicone gel-filled
implants are filled with silicone instead of saline. They were thought to cause
connective tissue disorders, but clear evidence of this has not been found.
Before having permanent implants, a woman may temporarily have a tissue
expander placed that will create the correct sized pocked for the implant. Talk

with your doctor about the benefits and risks of silicone versus saline implants.
Other important factors to consider when choosing implants include:
o Saline implants sometimes "crinkle" at the top or shift with time, but
many women don't find it bothersome enough to replace.
o Saline implants tend to feel different than silicone implants. They are
often firmer to the touch than silicone implants.
o There can be problems with breast implants. The implants can rupture or
break, cause pain and scar tissue around the implant, or get infected.
Some women may also have problems with the shape or appearance.
Although these problems are very unusual, talk with your doctor about
the risks.3
Tissue flap procedures. These techniques use muscle and tissue from
elsewhere in the body to reshape the breast. There are several flap procedures:
o Transverse rectus abdominis muscle (TRAM) flap. This method uses
muscle and tissue from the lower stomach wall.
o Latissimusdorsi flap, which uses muscle and tissue from the upper back.
o Deep inferior epigastric artery perforator (DIEP) flap. The DIEP flap
takes tissue from the abdomen and the surgeon attaches the blood
vessels to the chest wall.
o Gluteal free flap. The gluteal free flap uses tissue and muscle from the
buttocks to create the breast, and the surgeon also attaches the blood
vessels.

Because blood vessels are involved with flap procedures, they are usually not
recommended for a woman with a history of diabetes or connective tissue or
vascular disease, or for a woman who smokes, as the risk of problems during
and after surgery is much higher.
The DIEP and gluteal free flap procedures are longer procedures and the
recovery time is longer, but the appearance of the breast may be preferred,
especially when radiation therapy is part of the treatment plan.
Talk with your doctor for more information about reconstruction options. When
considering a plastic surgeon, choose a doctor who has experience with a variety of
reconstructive surgeries, including implants and flap procedures, and can discuss the
pros and cons of each procedure.3
External breast forms (prostheses)
An external breast prosthesis or artificial breast form provides an option for women
who plan to delay or not have reconstructive surgery. These can be made of silicone
or soft material, and fit into a mastectomy bra. Breast prostheses can be made to
provide a good fit and natural appearance for each woman.3
Treatment options for a local or regional breast cancer recurrence
A local or regional recurrence is often manageable and may be curable. The treatment
options are explained below:
For women with a local recurrence in the breast after initial treatment with
lumpectomy and adjuvant radiation therapy, the recommended treatment is
mastectomy. Usually the cancer is completely removed with this treatment.
For women with a local or regional recurrence in the chest wall after an initial
mastectomy, surgical removal of the recurrence followed by radiation therapy

to the chest wall and lymph nodes is the recommended treatment. However, if
radiation therapy has already been given for the initial cancer, this may not be
an option. Radiation therapy cannot usually be given at full dose to the same
area more than once.
Other treatments used to reduce the chance of a future distant recurrence
include radiation therapy, chemotherapy, hormonal therapy, and targeted
therapy. These are used depending on the tumor and the type of treatment
previously received.3
Whichever treatment plan you choose, palliative care will be important for relieving
symptoms and side effects. Your doctor may also suggest clinical trials that are
studying new ways to treat this type of recurrent cancer.3
8.COMPLIMENTARY AND ALTERNATIVE THERAPY
Complementary treatment refers to any type of care that you use along with
standard care.
Many complementary treatments may hold great value. But theres a lack of research
regarding their risks, benefits, side effects, and how they might interact with standard
care.
But research into CAM is growing. Complementary therapies are becoming part of
doctors' treatment options. And more and more doctors are recommending them to
patients.4
Alternative treatment refers to care that you use to replace standard care as an
alternative to the Western medical approach.4
How are complementary and alternative treatments developed?

Many of these therapies have roots in alternative medical systems. These systems
have different ways of understanding the human body, disease, and healing. As a
result, they differ, sometimes significantly, from Western medicine.
Most complementary and alternative treatments are forms of holistic medicine. That
means they seek to restore health and balance to the "whole person" -- not just the
body. They focus on your mind, emotions, and spirit, too.
Alternative medical systems include:

Traditional Chinese medicine, which uses acupuncture, tai chi, qigong, herbs,
and massage to unblock internal lines of energy that are believed to run through the
body.

Ayurvedic medicine, an ancient system from India. It seeks to harmonize mind,

body, and spirit through foods, meditation, and massage.

Naturopathy and homeopathy, which use herbs, botanicals, and other natural
products to help the body heal itself.

Indigenous healing methods, which have origins in the practices of Native

American, Hawaiian, or South American peoples. Each system has its own beliefs
about the cause of disease and healing.4
acupuncture
Some complementary treatments for cancer, such as acupuncture, have been
researched. A small study shows that acupuncture may help relieve hot flashes caused
by somebreast cancer treatments. Yoga, massage, and meditation have also been
shown to decrease these hot flashes. Other benefits of acupuncture may include less
vomiting, pain, and fatigue.

FIGURE 4:ACUPUNCTURE
Precautions: Women with lymph nodes removed under one arm shouldn't have
acupuncture needles inserted into that arm. That's because there is a risk of swelling
and excess fluid, a condition calledlymphedema. Also, women with severely
weakened immune systems are at higher risk of infection and should talk to their
doctor before undergoing acupuncture.4

tai chi and qigong

Many CAM therapies are based on the idea that a natural, vital "bioenergy" exists.
This energy is thought to cause health and healing, and disease happens when its
blocked or weakened.
Tai chi and qigong are both from China and are based on manipulating energy
through gentle movement, a focus on breathing, and meditation.

It's used as an addition to chemotherapy and radiation, and as a primary treatment for
people with inoperable, advanced cancer.4
More U.S. hospitals are offering tai chi as a complement to standard care. It can bring
an increase in self-esteem, an improvement in quality of life, and a sense of wellbeing.
Precautions: Because tai chi and qigong are so gentle, they carry few risks. You
should, however, talk with your doctor before beginning any new exercise program.4
reiki
Another form of energy medicine that is sometimes used in the treatment of breast
cancer is reiki, a practice that comes from Japan. Practitioners pass their hands over a
person's body to manipulate bioenergy. Most women who try reiki report feelings of
relaxation and reduced pain, but no research has yet proved its benefits or shown how
it works.
yoga
Yoga is being studied as a complementary treatment for breast cancer. Its been
shown to increase energy, vitality, and quality of life. Women with breast cancer -especially after surgery -- should look for a gentle style of yoga. For example, hatha
and restorative yoga may be good choices. These styles focus more on breathing,
gentle movement, and relaxation.4
Precautions: More athletic styles of yoga, such as power yoga, work the upper body.
Depending on the type of treatment, these may not be good for some women. If
youve had lymph nodes removed under one arm, theres a risk of lymphedema.
Always check with your doctor before starting any new exercise program, including
yoga.

 herbs, supplements, and botanicals help with breast cancer?

Antioxidants that have been studied to prevent or treat cancer include vitamins C and
E and co-enzyme Q10. Studies have not shown that they are helpful.
Precautions: Talk with your doctor before taking any vitamin, mineral, or herbal
supplements, especially in high doses. This includes garlic capsules, ginseng, ginkgo,
soy, and valerian. Some of these supplements can affect cancer treatment. For
example, St. John's wort, which is used for depression, can block certain cancer
drugs. High doses of vitamin C, an antioxidant, can change the way chemotherapy
and radiation affect your body.
Also, the safety, effectiveness, and manufacture of dietary supplements aren't
regulated as strictly as prescription medications.4
BIBLIOGRAPHY

1.Dunnwald LK, Rossing MA, Li CI. Hormone receptorstatus,tumor,characteristics,

and prognosis: a prospective cohort of breast cancer patients. Breast Cancer
Research2007; 9(1):R6
2.Sellwoood RA The definition of the no change category in patients treated with
endocrine therapy and chemotherapy for advanced carcinoma of the breast. Eur J
Cancer Clin Oncol1988;24:156772.
3.Clemons M and Goss P. Estrogen and the risk of breast cancer. NEJM 344(4): 276285, 2001.
4.Collaborative Group on Hormonal Factors in Breast Cancer: Breast cancer and
hormonal contraceptives: collaborative reanalysis of individual data on 53,297
women with breast cancer and 100,239 women without breast cancer from 54
epidemiological studies. Lancet 347(9017):1713-1727, 1996.