Stage III Breast Cancer

Overview
Stage III breast cancer is characterized by one of the following: A primary cancer that measures less than 5 cm ! inches" in size and causes a#illary underarm" lymph nodes to be attached to each other or other structures !. A primary cancer that is greater than 5 cm ! inches" in size and in$ol$es a#illary lymph nodes %. A primary cancer that is attached to the chest wall or s&in Breast cancer that has spread to the lymph nodes is commonly referred to as node'positi$e disease. (ffecti$e treatment of stage III breast cancer re)uires both local and systemic therapy. *ocal therapy consists of surgery and+or radiation and is directed at destroying any cancer cells in or near the breast. Systemic therapy is directed at destroying cancer cells throughout the body, and may include chemotherapy, hormonal therapy, or biological therapy. Systemic therapy may be administered before surgery, which is called neoad-u$ant therapy. .he following is a general o$er$iew of treatment for stage III breast cancer. /ulti'modality treatment, which utilizes two or more treatment techni)ues, is increasingly recognized as an important approach for impro$ing a patient0s chance of cure or prolonging sur$i$al. In some cases, participation in a clinical trial utilizing new, inno$ati$e therapies may pro$ide the most promising treatment. Circumstances uni)ue to each patient0s situation may influence how these general treatment principles are applied. .he potential benefits of multi'modality care, participation in a clinical trial, or standard treatment must be carefully balanced with the potential ris&s. .he information on this website is intended to help educate patients about their treatment options and to facilitate a mutual or shared decision'ma&ing process with their cancer physician. Local Therapy: Surgery and Radiation Systemic Therapy Chemotherapy Targeted Therapy Hormonal Therapy Strategies to Improve Treatment 1.

Local Therapy: Surgery and Radiation

Surgery and radiation are considered local therapies because they can treat the cancer in the breast and pre$ent cancer recurrence in the affected breast and surrounding area, but cannot treat cancer that has already spread to other locations in the body. Surgery: 1octors currently recommend that all patients with stage III breast cancer undergo surgical remo$al of the primary breast cancer. Surgery for stage III breast cancers may consist of mastectomy or lumpectomy. A mastectomy in$ol$es remo$al of the entire breast, whereas alumpectomy in$ol$es remo$al of the cancer and a portion of surrounding tissue. Because a lumpectomy alone is associated with a higher rate of cancer recurrence than mastectomy, patients who elect to ha$e a lumpectomy are also treated with radiation therapy. .his combination of lumpectomy and radiation therapy is called breast-conserving therapy. Clinical studies ha$e shown that breast'conser$ing therapy is associated with a lower ris& of local cancer recurrence compared to lumpectomy alone. ,! 2urthermore, breast'conser$ing therapy and mastectomy ha$e been shown to produce identical long'term sur$i$al." Some patients who are not initially candidates for breast'conser$ing therapy may become eligible for breast' conser$ing therapy after undergoing chemotherapy. Systemic treatment before surgery is called neoad-u$ant therapy. 3eoad-u$ant chemotherapy is a recommended treatment for some women with stage III breast cancer. 2or more information, go to neoad-u$ant chemotherapy.

Surgery for early stage breast cancer may also in$ol$e the e$aluation of a#illary underarm" lymph nodes to determine the stage of disease and whether cancer has spread outside the breast. 2or o$er %4 years, the standard of practice for breast cancer staging has included the remo$al of appro#imately 14'!5 a#illary lymph nodes to help determine whether the cancer has spread. .his procedure, called an a#illary lymph node dissection, can be associated with chronic side effects, including pain, limited shoulder motion, numbness, and swelling. A new approach for e$aluating whether cancer has spread to the lymph nodes is a sentinel lymph node biopsy . .he ad$antage to this procedure is that it in$ol$es the remo$al of a single lymph node, called the sentinel node, which is the first lymph node to collect e#cess fluid surrounding the cancer. 5rior to surgery, blue dye is in-ected near the cancer. .he dye drains from the area containing the cancer into the nearby lymph nodes, through the sentinel node. .he node containing the dye is remo$ed during surgery and e$aluated under a microscope to determine whether cancer has spread. Sentinel lymph node biopsy is becoming the standard approach for determining whether cancer has spread to the a#illary lymph nodes.# 6esearch now indicates that sentinel node biopsy appears to be $ust as e%%ective as an a&illary lymph node dissection in determining cancer spread to lymph nodes and results in %ewer side e%%ects in patients with stage II'III breast cancer.' 2or more detailed information, go to Surgery for Breast Cancer. Radiation therapy: It is recommended that patients with stage III breast cancers treated with lumpectomy breast' conser$ing surgery" recei$e additional treatment with radiation therapy. .he addition of radiation therapy decreases the ris& of local cancer recurrence and impro$es sur$i$al. Three studies have shown that the addition o% radiation therapy to mastectomy and chemotherapy reduces cancer recurrences and increases survival among women with stage II'III breast cancer. In a clinical study in$ol$ing 1,748 women with stage II'III breast cancer, researchers from 1enmar& reported a reduction in local regional recurrence, an increase in sur$i$al, and an increased probability of sur$i$ing 14 years or more with radiation therapy see .able 1". ( .able 1 Addition of radiation therapy to chemotherapy impro$es sur$i$al in the treatment of early stage breast cancer Chemotherapy plus radiation therapyChemotherapy alone

*ocal'regional recurrence Sur$i$al at 14 years 5robability of sur$i$ing 14 years or more

9: 5;: ;8:

%!: ;5: %;:

Canadian researchers reported that, among %19 women with node'positi$e breast cancer that were randomized to recei$e chemotherapy plus radiation or chemotherapy alone, !9: fewer patients died and cancer recurrences were reduced by %%: with the addition of radiation therapy.) 2inally, researchers from /.1. Anderson ha$e reported that radiation therapy following a mastectomy in patients with node'positi$e breast cancer appears to drastically reduce the rate of local'regional recurrences. .hese findings were based on e$aluation of the results from 5 clinical trials in$ol$ing appro#imately 1,544 women. .he outcomes of ;<9 women who recei$ed radiation therapy following a mastectomy were compared to the outcomes of 1,4%1 women who did not recei$e additional radiation therapy following a mastectomy. All patients were treated with Adriamycin= do#orubicin"'based chemotherapy. >omen with increasing lymph node in$ol$ement or cancer cells near the edge of the surgically remo$ed tissue appear to benefit most from post'mastectomy radiation.* Radiation therapy has also been shown to bene%it postmenopausal women with stage II-III breast cancer that receive hormonal therapy+ .he 1,%75 women in$ol$ed in this study were randomly assigned to recei$e hormonal

therapy for one year alone <89" or hormonal therapy with postoperati$e radiotherapy to the chest wall and regional lymph nodes <8<". 6esults showed a significant reduction in local regional recurrence and impro$ement in disease' free sur$i$al and sur$i$al of 14 years or more for patients who recei$ed radiation therapy see .able !"., .able ! Addition of radiation to hormonal therapy impro$es sur$i$al in the treatment of early stage breast cancer ?ormonal therapy plus radiation ?ormonal therapy alone

*ocal'regional cancer recurrence 1isease'free sur$i$al 14'year sur$i$al

8: %4: ;5:

%5: !;: %<:

Systemic Therapy: Chemotherapy- Targeted Therapy- and Hormonal Therapy

Systemic therapy is treatment directed at destroying cancer cells throughout the body. Some patients with stage III breast cancer already ha$e small amounts of cancer that ha$e spread outside the breast that the surgery or radiation does not treat. .hese cancer cells cannot be detected with any of the currently a$ailable tests and are referred to as micrometastases. .he presence of micrometastases causes breast cancer recurrence following local treatment with surgery and+or radiation therapy alone. An effecti$e systemic treatment is needed to cleanse the body of micrometastases in order to impro$e a patient0s duration of sur$i$al and potential for cure. (#amples of systemic therapies that are commonly used in the treatment of stage III breast cancer include:

Chemotherapy .argeted .herapy ?ormonal .herapy

2urthermore, some patients who are not initially candidates for breast'conser$ing therapy may become eligible for this treatment after undergoing chemotherapy. Systemic treatment before surgery is called neoad-u$ant therapy. 3eoad-u$ant chemotherapy is the recommended systemic therapy for many women with stage III breast cancer.

Chemotherapy
Chemotherapy is any treatment in$ol$ing the use of drugs to &ill cancer cells and is a standard ad-u$ant therapy for the treatment of early stage breast cancer. Cancer chemotherapy may consist of single drugs or combinations of drugs and can be administered through a $ein or deli$ered orally in the form of a pill. ?istorically, systemic therapy has been administered after surgery and is referred to as ad-u$ant therapy. Clinical trials ha$e shown that ad-u$ant chemotherapy impro$es a patient0s chance of sur$i$al and decreases the ris& of cancer recurrence compared to local therapy alone in the treatment of stage III breast cancer. . Chemotherapy options: .here are many different chemotherapy drugs and combinations of drugs regimens". .he regimen consisting of cyclophosphamide, methotre#ate and fluorouracil C/0 " was the first standard combination used to treat indi$iduals with early stage breast cancer and has been in use for many years. C/2 chemotherapy is typically administered for < cycles o$er a period of appro#imately ;'< months. 6esearch shows that the inclusion of the chemotherapy drug do&orubicin in ad$uvant chemotherapy increases the number o% women that can e&pect to survive without evidence o% cancer compared to combination chemotherapy without do#orubicin. ! C10 cyclophosphamide, do#orubicin, and fluorouracil" and 1C do#orubicin and cyclophosphamide" are also considered standard chemotherapy regimens for the treatment of early stage breast cancer. ?owe$er, these regimens are typically associated with more side effects than C/2+ Ta&anes: .he ta#anes are a class of chemotherapy drug that ha$e been shown to impro$e cancer'free sur$i$al in women with stage II'III breast cancer. " .a#otere= doceta#el" appears to be more effecti$e than paclita#el in the treatment of patients with ad$anced breast cancer. # .he ta#anes are typically combined with AC chemotherapy.

Ta&otere-containing combinations: 5atients treated with a combination of .a#otere, do#orubicin, and cyclophosphamide@called T1C@ha$e been shown to li$e longer and are cancer'free longer than those treated with 2AC 5'fluorouracil, do#orubicin, cyclophosphamide". .his trial in$ol$ed 1,544 women with node'positi$e, early stage II'III" breast cancer see .able %". ' .able % .a#otere'containing chemotherapy .AC" impro$es sur$i$al o$er standard regimen 2AC" .AC 2AC

Cancer'free sur$i$al A$erall sur$i$al

75: 87:

<8: 81:

5atients treated with Ta&otere and cyclophosphamide ha$e been shown to be free of cancer for longer after treatment compared to patients treated with standard AC. 2urthermore .a#otere+cyclophosphamide may be less to#ic to the heart. ( 2ose-dense chemotherapy: AC, .AC, C/2 and other chemotherapy regimens are typically administered e$ery % wee&s. 1ose'dense chemotherapy refers to chemotherapy treatment that is administered more fre)uently. 1ose' dense treatment is gi$en e$ery ! wee&s rather than at the con$entional %'wee& inter$al in order to increase the total amount of chemotherapy used to treat the cancer. 6esearchers ha$e reported that patients with node'positi$e breast cancer treated with dose'dense chemotherapy li$e longer without cancer recurrence than patients treated with con$entional chemotherapy. .he !,445 patients in$ol$ed in one study recei$ed chemotherapy treatment with do#orubicin, paclita#el, and cyclophosphamide either e$ery % wee&s con$entional treatment" or e$ery ! wee&s dose'dense". At ; years, 8!: of patients treated with dose'dense therapy were disease'free, compared to 75: of those treated with con$entional chemotherapy. ) 3eoad$uvant chemotherapy: 3eoad-u$ant therapy is treatment administered before surgery. .he purpose of neoad-u$ant therapy is to immediately treat and shrin& the cancer in order to increase the li&elihood that it may be completely remo$ed with surgery. A committee of physicians, called .he Consensus Conference Committee, has published treatment guidelines stating that neoad-u$ant chemotherapy is Bthe treatment of choiceC for patients with stage III breast cancer and is Bworthy of considerationC in patients with stage IIA and IIB breast cancer. *.he committee0s guidelines are determined by an e#tensi$e re$iew of clinical studies that e$aluated neoad-u$ant chemotherapy in different stages of breast cancer. Although the long'term benefits of neoad-u$ant chemotherapy are currently un&nown, the results of clinical trials clearly demonstrate that neoad-u$ant therapy increases the li&elihood that patients can undergo breast'conser$ing surgical treatment instead of surgical mastectomy. , 6esearchers affiliated with the 3ational Surgical Ad-u$ant Breast and Bowel 5ro-ect ha$e reported that neoad$uvant chemotherapy that includes the drug Ta&otere produces more anti-cancer responses than neoad-u$ant chemotherapy without .a#otere or neoad-u$ant chemotherapy combined with ad-u$ant .a#otere. .his trial in$ol$ed o$er !,444 women who were randomly assigned to recei$e one of the following treatments: 3eoad-u$ant AC do#orubicin plus cyclophosphamide" 3eoad-u$ant AC plus .a#otere 3eoad-u$ant AC plus .a#otere after surgery Appro#imately 91: of the patients treated with .a#otere= before surgery had an anti'cancer response, compared to 85: of patients in the other two groups.!.

Targeted Therapy
A targeted therapy is one that is designed to treat only the cancer cells and minimize damage to normal, healthy cells. Cancer treatments that BtargetC cancer cells may offer the ad$antage of reduced treatment'related side effects and impro$ed outcomes.

Con$entional cancer treatments, such as chemotherapy and radiation therapy, cannot distinguish between cancer cells and healthy cells. Conse)uently, healthy cells are commonly damaged in the process of treating the cancer, which results in side effects. Chemotherapy damages rapidly di$iding cells, a hallmar& trait of cancer cells. In the process, healthy cells that are also rapidly di$iding, such as blood cells and the cells lining the mouth and DI tract are also damaged. 6adiation therapy &ills some healthy cells that are in the path of the radiation or near the cancer being treated. 3ewer radiation therapy techni)ues can reduce, but not eliminate this damage. .reatment'related damage to healthy cells leads to complications of treatment, or side effects. .hese side effects may be se$ere, reducing a patient0s )uality of life, compromising their ability to recei$e their full, prescribed treatment, and sometimes, limiting their chance for an optimal outcome from treatment. /onoclonal antibodies: Ad$ances in science and technology ha$e led to the de$elopment of se$eral different types of targeted therapies. /onoclonal antibodies are a type of targeted therapy that has been used in the treatment of breast cancer. /onoclonal antibodies are comprised of proteins that can be made in the laboratory and are designed to recognize and bind to specific proteins that occur in large )uantities on the surface of some cancer cells. .his binding action promotes anti'cancer benefits by: (liminating the cancer cell0s stimulus to grow, and Acti$ating the immune system to attac& and &ill the cancer cells that the monoclonal antibody is bound to. Human 4pidermal 5rowth 0actor Receptor ! 6H4R!7: Some breast cancers ha$e an abundance of a protein called ?(6! on their outer surface. .hese cancers are called ?(6!'positi$e. ?(6! proteins bind e#clusi$ely with other proteins that circulate in the blood called growth factors. .his binding acti$ity leads to the uncontrolled replication and growth of the cancer cells. Appro#imately one out of three breast cancer patients ha$e ?(6!'positi$e breast cancer.! Herceptin8: ?erceptin trastuzumab" is a monoclonal antibody that binds to the ?(6! protein. 6esults from an important clinical trial indicate that adding ?erceptin to chemotherapy impro$es sur$i$al for patients with ad$anced ?(6!'positi$e breast cancer.!! ?erceptin is the first monoclonal antibody to be appro$ed by the 21A for the treatment of ad$anced breast cancer and is also being e$aluated in the treatment of early stage breast cancer. 6esearchers reported in mid'!445 that women with node'positi$e breast cancer treated with chemotherapy plus ?erceptin had a significantly reduced ris& of death or cancer recurrence compared to patients treated with chemotherapy alone. .he researchers conducted large clinical trials in$ol$ing %,444 women who had positi$e lymph nodes or were considered to be high'ris& despite ha$ing no cancer spread to lymph nodes, and had recei$ed no pre$ious treatment with either anthracycline or ta#ane chemotherapy. 5atients recei$ed chemotherapy treatment consisting of do#orubicin and paclita#el with or without ?erceptin. After two years of treatment, results indicate that patients who received Herceptin had a ""9 reduced ris: o% dying compared to patients that recei$ed chemotherapy alone. Also, the rate of acancer recurrence was reduced by '!9 in patients treated with Herceptin .!"

Hormonal Therapy
?ormonal therapy in$ol$es reducing the le$el of estrogen in the body. (strogen is an essential female hormone that is produced by the o$aries and adrenal glands. It ser$es many critical functions in the body, including de$eloping the female se# organs in puberty, preparing the breasts and uterus for pregnancy in adulthood, and maintaining cardio$ascular and bone health. >ithout estrogen, the female body is unable to sustain pregnancy and is susceptible to heart disease and osteoporosis. (strogen can also cause some cancers to grow. .he breasts, uterus and other female organs are composed of cells that are stimulated to grow when e#posed to estrogen. .hese cells ha$e estrogen receptors on their surface. (strogen circulating in the blood binds to these receptors and stimulates growth'related acti$ities in the cell. >hen cells that ha$e estrogen receptors become cancerous, e#posure to estrogen increases the cancer0s growth. Cancer cells that ha$e estrogen receptors are referred to as estrogen receptor'positi$e (6'positi$e" cancers.

.he growth of (6'positi$e breast cancer cells can be pre$ented or slowed by reducing the e#posure to estrogen. .his is the goal of hormonal therapy for breast cancer. ?owe$er, a reduction in estrogen le$els can also result in side effects because estrogen is necessary for important body functions, such as bone growth and cardio$ascular health. *ower estrogen le$els lead to decreased bone density and heart disease. ?ormonal therapy appears to benefit all women with early stage breast cancer. .he hormonal therapies that ha$e been in$estigated in the treatment of early stage breast cancer are:

.amo#ifen Anti'aromatase drugs

2urthermore, there is some e$idence that patients who ha$e been treated with tamo#ifen for !'5 years may benefit from switching to an anti'aromatase drug.!#,!' Tamo&i%en %or 4arly Stage ;reast Cancer .he results of se$eral clinical studies indicate that hormonal treatment with tamo#ifen, either alone!( or in combination with chemotherapy!),!*,!,,". can reduce the rate of cancer recurrence and impro$e the duration of sur$i$al in women with (6'positi$e breast cancer. 5atients with (6'status'un&nown breast cancer may also benefit, but tamo#ifen does not appear to be a beneficial treatment for patients with (6'negati$e breast cancer. ?owe$er, (6'negati$e patients are at high ris& of de$eloping a cancer in their other breast and may want to learn more about pre$ention of breast cancer using hormonal treatment." It is currently recommended that patients recei$e tamo#ifen for 5 years. 1nti-1romatase 2rugs %or 4arly Stage ;reast Cancer Anti'aromatase drugs ha$e been shown to pro$ide a greater reduction in the ris& of cancer recurrence and appear to produce fewer side effects than tamo#ifen. .he anti'aromatase drugs that are appro$ed for the treatment of early stage breast cancer include 1rimide&8 anastrazole" and 0emara8 letrozole". Ane of the most notable studies designed to e$aluate the use of an anti'aromatase drug in the management of early stage breast cancer was the Arimide#, .amo#ifen Alone or in Combination A.AC" clinical trial. In this clinical trial, o$er 9,444 post'menopausal women with (6'positi$e or un&nown receptor status, early stage breast cancer were treated with either Arimide#, tamo#ifen, or both drugs as ad-u$ant therapy for fi$e years and the results were then directly compared. After !.5 years of treatment, patients treated with the anti'aromatase drug Arimide# had a 17: decrease in the ris& of cancer recurrence compared to patients treated with tamo#ifen."! After ; years of treatment, (6'positi$e and (6 status un&nown patients treated with 1rimide&8 were more li:ely to be alive without cancer recurrence than patients treated with tamo&i%en . In addition, the rate of breast cancer in the opposite breast was reduced by half in patients treated with Arimide# compared to patients treated with tamo#ifen. 5atients treated with tamo#ifen were more li&ely to de$elop uterine cancer, $aginal bleeding, stro&e, blood clots and hot flashes, while patients treated with Arimide# e#perienced more musculos&eletal problems and bone fractures."" Should patients switch from tamoxifen to an anti-aromatase drug? Because the anti'aromatase agents appear to be superior to tamo#ifen, physicians ha$e conducted clinical trials to determine whether patients on tamo#ifen should switch to an anti'aromatase drug. Arimide# has been shown to pro$ide benefit following tamo#ifen in the treatment of patients with early stage breast cancer. 6esearch is ongoing to directly compare these post'tamo#ifen options and determine which treatment pro$ides the best outcomes. Switching from tamo#ifen to Arimide# has also been shown to reduce cancer recurrence. Ane study e$aluated o$er ;44 postmenopausal women with (6'positi$e breast cancer who had already been treated with tamo#ifen for at least ! years. 5atients either continued with tamo#ifen for up to 5 years or switched to Arimide# for a comparable amount of time."# .he patients who switched to Arimide# had <4: fewer cancer recurrences than patients who remained on tamo#ifen. How long should patients take hormonal therapy?

.amo#ifen has been the standard drug for hormonal therapy and is typically administered for 5 years. 6esearch is ongoing to determine if patients can benefit from more than 5 years of hormonal therapy. 2emara has been shown to pro$ide a reduced ris& of death and cancer recurrence when used after 5 years of tamo#ifen. A$er 5,444 postmenopausal women who had completed 5 years of treatment with tamo#ifen participated in a clinical trial e$aluating 2emara. Appro#imately half of these women recei$ed 2emara and the other half recei$ed a placebo inacti$e substance". A$erall, treatment with 2emara reduced the ris& of cancer recurrence by ;4:. >omen with node'positi$e disease that were treated with 2emara had a %9: reduced ris& of death compared to patients who recei$ed placebo. Appro#imately 5: of the patients treated with 2emara e#perienced a reduced )uality of life compared to those treated with placebo. .his included decreased physical function <:", increased pain 5:", and decreased $itality 5:". ?owe$er, a large proportion of patients considered the side effects to be worth the reduced ris& of a cancer recurrence. .his trial was stopped prematurely due to the ob$ious benefits of treatment with 2emara compared to placebo."' What is the optimal sequence of therapy? .he timing or se)uence of therapy may be important. A large clinical study has addressed the )uestion of whether radiation therapy should be gi$en before or after chemotherapy following treatment with breast'conser$ing surgery. 2ollowing breast'conser$ing surgery, half the patients in this study were treated with chemotherapy followed by radiation and half were treated with radiation followed by chemotherapy. .he patients treated with chemotherapy followed by radiation were more li&ely to li$e 5 years or more after treatment than patients treated with radiation followed by chemotherapy. 5atients treated with chemotherapy first sur$i$ed longer because they were less li&ely to e#perience systemic recurrence of their cancer. 5atients treated with radiation first, howe$er, were less li&ely to e#perience a local recurrence of their cancer."( It is much easier to treat local recurrence of cancer than systemic recurrence of cancer and this may e#plain why the patients treated with chemotherapy followed by radiation had impro$ed sur$i$al compared to patients treated with radiation followed by chemotherapy. An additional e#planation is that deli$ering radiation therapy before chemotherapy treatment of systemic disease may ad$ersely affect the doctor0s ability to deli$er the chemotherapy treatment. Although the se)uence of treatments is undergoing continued e$aluation, the current data suggest that standard treatment of early stage breast cancer outside the conte#t of a clinical study should include definiti$e surgery first, followed by systemic chemotherapy, and lastly, radiation. ?ormone therapy can begin during or following radiation therapy.

Strategies to Improve Treatment

.he de$elopment of more effecti$e cancer treatments re)uires that new and inno$ati$e therapies be e$aluated with cancer patients. Clinical trials are studies that e$aluate the effecti$eness of new drugs or treatment strategies. 2uture progress in the treatment of stage III breast cancer will result from the continued e$aluation of new treatments in clinical trials. 5articipation in a clinical trial may offer patients access to better treatments and ad$ance the e#isting &nowledge about treatment of this cancer. 5atients who are interested in participating in a clinical trial should discuss the ris&s and benefits of clinical trials with their physician. Areas of acti$e in$estigation aimed at impro$ing the treatment of stage III breast cancer include the following:

3ew ?ormonal .herapy 1rugs Ad$ances in 6adiation .herapy Brachytherapy Boost 6adiation

3ew Hormonal Therapy 2rugs

Se$eral newer hormonal therapies, called anti'aromatase drugs, ha$e pro$en to be superior to the once standard hormonal therapy drug tamo#ifen for the treatment of patients with (6'positi$e breast cancer."),"* .he anti' aromatase drugs also appear to be associated with fewer side effects.", Anti'aromatase drugs are a class of hormonal drugs that wor& by inhibiting the formation of estrogen in the body. Aromatase is the enzyme protein" that initiates the process through which hormones in the body are con$erted to estrogen. Anti'aromatase drugs wor& by inhibiting aromatase. .his acti$ity bloc&s the con$ersion of estrogens into their acti$e form and reduces le$els of acti$e estrogen in the body. In contrast, tamo#ifen bloc&s estrogen from entering a cell by directly binding to the cell0s estrogen receptors.

3ew 1pproaches to Radiation

;rachytherapy: Ad$ances in radiation therapy ha$e led to the de$elopment of an alternati$e to e#ternal beam radiation therapy (B6." called brachytherapy. Brachytherapy is a techni)ue for deli$ering radiation internally by implanting a radioacti$e material directly into or near the cancer. Brachytherapy does not in$ol$e daily $isits to a radiation facility, as the implants also called seeds" are left in the body for the duration of treatment. In addition, the total deli$ery time, or e#posure to radiation, is reduced with brachytherapy se$eral days" compared to standard e#ternal'beam radiation therapy se$eral wee&s". A clinical trial published in the Eournal of the 3ational Cancer Institute shows that brachytherapy appears to be -ust as effecti$e and more con$enient than (B6. for patients with early stage breast cancer. 2i$e years following administration of brachytherapy to 199 women with early stage breast cancer, 1: of the patients had a local cancer recurrence and 1: had a regional recurrence. Cancer spread to distant sites in the body occurred in 5: of patients and appro#imately %: of patients had died from breast cancer. .hese results were similar to data from a similar group of patients who underwent (B6..#. Radiation <boost= therapy: Standard radiation therapy following a lumpectomy consists of a limited dose of radiation 54 Dy" to the entire affected breast. >hile this treatment leads to long'term outcomes similar to those from mastectomy, women under age 54 e#perience higher rates of local recurrences following this treatment regimen compared to their elder counterparts. 6esearchers ha$e theorized that an additional boost of radiation aimed only at the area from which the cancer was remo$ed could reduce the rates of local recurrences, especially in younger patients. .he (uropean Arganization for 6esearch and .reatment of Cancer has reported that an additional dose of radiation to the site of the remo$ed cancer reduces local recurrence by nearly 54: among women with stage I or II breast cancer. .he 5,%18 women in$ol$ed in this trial had undergone a lumpectomy followed by the standard dose of radiation. Appro#imately half of the patients were gi$en an additional small dose of radiation to the area where the cancer had been located, while the other half recei$ed no additional treatment. .he researchers followed the women for an a$erage of 5.! years. >omen ;4 years old and younger e#hibited the largest benefitF in this group, local recurrences occurred in only 14.!: of patients recei$ing additional radiation, compared to 19.5: of those recei$ing standard treatment. A$erall sur$i$al rates and the de$elopment of distant metastases were similar whether women recei$ed an additional boost of radiation or standard therapy. Side effects including cosmetic results and fibrosis formation of scar tissue" were not affected by the additional radiation.#

Re%erences
2isher B, Anderson S, Bryant E, et al. .wenty'year follow'up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of in$asi$e breast cancer.3 (ngl E /ed. !44!F%;7:1!%%'1!;1. ! *ichter AS, *ippman /(, Er 1anforth 13, et al. /astectomy $ersus breast'conser$ing therapy in the treatment of stage I and II carcinoma of the breast: a randomized trial at the 3ational Cancer Institute. Eournal of Clinical Ancology, Classic 5apers and Current Comments. 199<F1:!'14.

" Geronesi H, Cascinelli 3, /ariani *, et al. .wenty'year follow'up of a randomized study comparing breast' conser$ing surgery with radical mastectomy for early breast cancer. 3 (ngl E /ed. !44!F%;7F1!!7'1!%!. # (dge SB, 3iland EC, Boo&man /A, et al. (mergence of sentinel node biopsy in breast cancer as standard'of care in academic comprehensi$e cancer centers. Eournal of the 3ational Cancer Institute. !44%F95:151;'15!1. ' Geronesi H, 5aganelli D, Giale D, et al. A randomized comparison of sentinel'node biopsy with routine a#illary dissection in breast cancer. 3 (ngl E /ed. !44%F%;9:5;<'55%. ( A$ergaard /, ?ansen 5S, A$ergaard E, et al. 5ostoperati$e 6adiothearpy in ?igh'6is& 5remenopausal >omen with Breast Cancer who 6ecei$e Ad-u$ant Chemotherapy. 3 (ngl E /ed. 1997F%%7 1;":9;9'955. ) 6agaz E, Stewart /E, 3hu *, et al. Ad-u$ant 6adiotherapy and Chemotherapy in 3ode'5ositi$e 5remenopausal >omen with Breast Cancer. 3 (ngl E /ed. 1997F%%7 1;":95<'9<!. * >oodward >, Iatz A, Buchholz ., et al. 5atterns and predictors of locoregional recurrence in ;<9 patients treated with post'mastectomy radiation. International Eournal of 6adiation Ancology, Biology and 5hysics. !44!F5;:91'9!. 5roceedings from the American Society of .herapeutic 6adiation Ancology. Abstract J158. , A$ergaard /, Eensen /'B, A$ergaard E, et al. 5ostoperati$e radiotherapy in high'ris& postmenopausal breast' cancer patients gi$en ad-u$ant tamo#ifen: 1anish Breast Cancer Cooperati$e Droup 1BCD 8!c randomised trial. *ancet. 1999F%5%:1<;1'1<;8. . Systemic treatment of early breast cancer by hormonal, cytoto#ic, or immune therapy. 1%% randomised trials in$ol$ing %1,444 recurrences and !;,444 deaths among 75,444 women. (arly Breast Cancer .rialists0 Collaborati$e Droup. *ancet. 199!F%%9:1'15. Bonadonna D, Brusamolino (, Galagussa 5, et al. Combination chemotherapy as an ad-u$ant treatment in operable breast cancer. 3 (ngl E /ed. 197<F!9;:;45';14. ! Cummings S6, 3orton *, (c&ert S, et al. 6alo#ifene reduces the ris& of breast cancer and may decrease the ris& of endometrial cancer in post'menopausal women. .wo'year findings from the /ultiple Autcomes of 6alo#ifene ($aluation /A6(" .rial. 5roceedings of American Society of Clinical Ancology 1998F17:Abstract J%. " 3abholtz E'/, 5ien&ows&i ., /ac&ey E, et al. 5hase III trial comparing .AC doceta#el, do#orubicin, cyclophosphamide" with 2AC 5'fluorouracil, do#orubicin, cyclophosphamide" in the ad-u$ant treatment of node positi$e breast cancer BC" patients: interim analysis of the BCI6D 441 study. 5roceedings from the %8th Annual /eeting of the American Society of Clinical Ancology. !44!F!1:Abstract J1;1. # Sparano EA, >ang /, /artino S, et al. 5hase III study of do#orubicin'cyclophosphamide followed by paclita#el or doceta#el gi$en e$ery % wee&s or wee&ly in patients with a#illary node'positi$e or high'ris& node'negati$e breast cancer: 6esults of the 3orth American Breast Cancer Intergroup .rial (1199. 5rogram and abstracts of the !8th Annual San Antonio Breast Cancer Symposium. !445FAbstract J;8. ' /artin /, 5ien&ows&i ., Eohn /ac&ey, et al. Ad-u$ant 1oceta#el for 3ode'5ositi$e Breast Cancer. 3ew (ngland Eournal of /edicine. !445F%5! !!":!%4!'!%1%. ( Eones S, Sa$in /, ?olmes 2, et al. 2inal analysis: .C doceta#el+cyclophosphamide, ; cycles" has a superior disease'free sur$i$al compared to standard AC do#orubicin+cyclophosphamide" in 141< women with early breast cancer. 5roceedings from the !8th San Antonio Breast Cancer Symposium. 1ecember !445FAbstract J;4. ) Citron /*, Berry 1A, Cirrincione C, ?udis C, et al. 6andomized trial of dose'dense $ersus con$entionally scheduled and se)uential $ersus concurrent combination chemotherapy as postoperati$e ad-u$ant treatment of node' positi$e primary breast cancer: 2irst report of intergroup trial C97;1+Cancer and *eu&emia Droup B trial 97;1. Eournal of Clinical Ancology. !44%F!1:1;%1'9. * Schwartz D2, ?ortobagyi D3 and the Consensus Conference Committee. 5roceedings of the Consensus Conference on 3eoad-u$ant Chemotherapy in Carcinoma of the Breast, 5hiladelphia 5A. Cancer. !44;F144:!51!' !5%!. , 2isher B, Brown A, /amounas (, et al. (ffect of preoperati$e chemotherapy on local'regional disease in women with operable breast cancer: findings from 3ational Surgical Ad-u$ant Breast and Bowel 5ro-ect B'18. Eournal of Clinical Ancology. 1997F15:!;8%'!;9%.

!. Bear ?1, Anderson S, Brown A, et al. .he (ffect on .umor 6esponse of Adding Se)uential 5reoperati$e 1oceta#el to 5reoperati$e 1o#orubicin and Cyclophosphamide: 5reliminary 6esults 2rom 3ational Surgical Ad-u$ant Breast And Bowel 5ro-ect 5rotocol B'!7. Eournal of Clinical Ancology. !44%F!1:;1<5';17;. ! 5ietras 6E, 2endly B/, Chazin G6, et al: Antibody to ?(6'!+neu receptor bloc&s 13A repair after cisplatin in human breast and o$arian cancer cells. Ancogene. 199;F9:18!9'18%8. !! Slamon 1E, *eyland'Eones B, Sha& S, 2uchs ?, 5aton G, Ba-amonde A, et al. Hse of chemotherapy plus a monoclonal antibody against ?(6! for metastatic breast cancer that o$ere#presses ?(6!. 3 (ngl E /ed !441F%;;:78%'79!. !" 6omond (, 5erez (, Bryant E, et al. 1o#orubicin and cyclophosphamide followed by paclita#el with or without trastuzumab as ad-u$ant therapy for patients with ?(6'! positi$e operable breast cancer. Combined analysis of 3SAB5 B1%+3CC.D 39%1. 5roceedings from the ;1st annual meeting of the American Society of Clinical Ancology, Arlando 2*. !445F *ate brea&ing abstract a$ailable at: http:++www.asco.org+ac+1,144%,K1!'44!511'44K18'44%;' 44K19'445817'44K!1'441,44.asp. !# Doss 5, Ingle E, /artino S, et al. Hpdated analysis of the 3CIC C.C /A.17 randomized placebo 5" controlled trial of letrozole *" after fi$e years of tamo#ifen in postmenopausal women with early stage breast cancer. 5roceedings from the ;4th annual meeting of the American Society of Clinical Ancology. 3ew Arleans *A. !44;F Abstract J8;7. !' Doss, et al. A randomized trial of letrozole in postmenopausal women after fi$e years of tamo#ifen therapy for early'stage breast cancer. 5roceedings from the !44% San Antonio Breast Cancer Symposium. !44%. !( /uss ?B. 6ole of ad-u$ant endocrine therapy in early'stage breast cancer. Seminars in Ancology. !441F!8:%1%' %!1. !) (arly Breast Cancer .rialists0 Collaborati$e Droup: A$arian ablation in early breast cancer: A$er$iew of the randomised trials. *ancet. 199<F%;8: 1189'119<. !* 2isher B, 6edmond C, *egault'5oisson S, et al. 5ostoperati$e chemotherapy and 3ol$ade#= compared with 3ol$ade#= alone in the treatment of positi$e'node breast cancer patients aged 54 years and older with tumors responsi$e to 3ol$ade#=: 6esults from the 3ational Surgical Ad-u$ant Breast and Bowel 5ro-ect B'1<. Classic 5apers and Current Comments. 199<F1:71'8;. !, International Breast Cancer Study Droup. (ffecti$eness of ad-u$ant chemotherapy in combination with 3ol$ade#= for node'positi$e postmenopausal breast cancer patients. E Clin Ancol. 1997F15:1%85'1%9;. ". 2isher B, 1ignam E, 1eCillis A, et al. .he worth of chemotherapy and 3ol$ade#= .A/" o$er .A/ alone in node' negati$e patients with estrogen'receptor (6" positi$e in$asi$e breast cancer BC": first results from 3SAB5 B'!4. 5roceedings of American Society of Clinical Ancology. 1997F1<:Abstract J1. " *i CI, /alone I(, >eiss 3S. 3ol$ade#= therapy for primary breast cancer and ris& of contralateral breast cancer. Eournal of the 3ational Cancer Institute. !441F1%:9<%'9<5. "! Baum /, on behalf of the A.AC .rialists0 Droup. .he A.AC Arimide#, 3ol$ade#, alone or in combination" ad-u$ant breast cancer trial in post'menopausal women. !;th annual San Antonio Breast Cancer Symposium. !441. "" .he A.AC Arimide#, tamo#ifen alone or in combination" trialists0 group. Anastrozole alone or in combination with tamo#ifen $ersus tamo#ifen alone for ad-u$ant treatment of postmenopausal women with early'stage breast cancer. Cancer. !44%F98 9":184!'1814. "# Boccardo 2, 6ubagotti A, Amoroso 1, et al. Anastrozole appears to be superior to tamo#ifen in women already recei$ing ad-u$ant tamo#ifen treatment. 5roceedings from the !44% San Antonio Breast Cancer Symposium, !44%FAbstract J%. "' Doss 5, Ingle E, /artino S, et al. Hpdated analysis of the 3CIC C.C /A.17 randomized placebo 5" controlled trial of letrozole *" after fi$e years of tamo#ifen in postmenopausal women with early stage breast cancer. 5roceedings from the ;4th annual meeting of the American Society of Clinical Ancology BBest of oncology symposiumC, 3ew Arleans, *A. !44;F Abstract J8;7. "( 6echt A, Come S(, ?enderson IC, et al. .he se)uencing of chemotherapy and radiation therapy after conser$ati$e surgery for early'stage breast cancer. 3 (ngl E /ed. 199<F%%;:1%5<'1%<1.

") /ouridsen ?, Dershano$ich /, Sun L, et al. 5hase III Study of *etrozole Gersus .amo#ifen as 2irst'*ine .herapy of Ad$anced Breast Cancer in >omen: Analysis of Sur$i$al and Hpdate of (fficacy 2rom the International *etrozole Breast Cancer Droup. Eournal of Clinical Ancology. !44%F!1:!141'!149. "* Bonneterre E, Buzdar A, 3abholtz E'/ A, et al.: Anastrozole is superior to tamo#ifen as first'line therapy in hormone receptor positi$e ad$anced breast carcinoma: 6esults of two randomized trials designed for combined analysis. Cancer. !441F9!:!!;7'!!58. ", .he A.AC Arimide#, tamo#ifen alone or in combination" trialists0 group. Anastrozole alone or in combination with tamo#ifen $ersus tamo#ifen alone for ad-u$ant treatment of postmenopausal women with early'stage breast cancer. Cancer. !44%F98 9":184!'1814. #. Gicini 2, Iestin *, Chen 5, et al. *imited field radiation therapy in the management of early'stage breast cancer. Eournal of the 3ational Cancer Institute. !44%F95:1!45'1!11. # Bartelin& ?, ?oriot E'C, 5oortmans 5, et al. 6ecurrence rates after treatment of breast cancer with standard radiotherapy with or without additional radiation. 3 (ngl E /ed. !441F%;5:1%78'1%87.

TR41TI35 ;R41ST C13C4R TO>ICS 1ocument .opics

DA M

S(( A *IS. M

>revious Topic

Radiation therapy %or breast cancer

3e&t Topic

Hormone therapy %or breast cancer

Chemotherapy %or breast cancer

Chemotherapy chemo" is treatment with cancer'&illing drugs that may be gi$en intra$enously in-ected into a $ein" or by mouth. .he drugs tra$el through the bloodstream to reach cancer cells in most parts of the body. Chemo is gi$en in cycles, with each period of treatment followed by a reco$ery period. .reatment usually lasts for se$eral months. If you0d li&e more information on a drug used in your treatment or a specific drug mentioned in this section, see ourDuide to Cancer 1rugs , or call us with the names of the medicines you0re ta&ing.

?hen is chemotherapy used@

.here are se$eral situations in which chemo may be recommended. 1%ter surgery 6ad$uvant chemotherapy7: >hen therapy is gi$en to patients with no e$idence of cancer after surgery, it is called adjuvant therapy. Surgery is used to remo$e all of the cancer that can be seen,

but ad-u$ant therapy is used to &ill any cancer cells that may ha$e been left behind but canNt be seen. Ad-u$ant therapy after breast'conser$ing surgery or mastectomy reduces the ris& of breast cancer coming bac&. 6adiation, chemo, targeted therapy, and hormone therapy can all be used as ad-u$ant treatments. ($en in the early stages of the disease, cancer cells may brea& away from the primary breast tumor and spread through the bloodstream. .hese cells donNt cause symptoms, they donNt show up on imaging tests, and they canNt be felt during a physical e#am. But if they are allowed to grow, they can establish new tumors in other places in the body. .he goal of ad-u$ant chemo is to &ill undetected cells that ha$e tra$eled from the breast. ;e%ore surgery 6neoad$uvant chemotherapy7: Chemo gi$en before surgery is called neoadjuvant chemotherapy. Aften, neoad-u$ant therapy uses the same treatments that are used as ad-u$ant therapy, only they are gi$en or at least started" before surgery instead of after. In terms of sur$i$al, there is no difference between gi$ing chemo before or after surgery. .he ma-or benefit of neoad-u$ant chemo is that it can shrin& large cancers so that they are small enough to be remo$ed with less e#tensi$e surgery. .he other ad$antage of neoad-u$ant chemo is that doctors can see how the cancer responds to the chemo drugs. If the tumor does not shrin& with the first set of drugs, your doctor will &now that other chemo drugs are needed. Some breast cancers are too big to be surgically remo$ed at the time of diagnosis. .hese cancers are referred to aslocally advanced and ha$e to be treated with chemo to shrin& them so they can be remo$ed with surgery. 0or 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. .he length of treatment depends on whether the cancer shrin&s, how much it shrin&s, and how a woman tolerates treatment.

How is chemotherapy given@

In most cases especially ad-u$ant and neoad-u$ant treatment", chemo is most effecti$e when combinations of more than one drug are used. /any combinations are being used, and itNs not clear that any single combination is clearly the best. Clinical studies continue to compare todayNs most effecti$e treatments against something that may be better. .he most common chemo drugs used for early breast cancer include the anthracyclines such as do#orubicin+Adriamycin and epirubicin+(llence" and the ta#anes such as paclita#el+.a#ol and doceta#el+.a#otere". .hese may be used in combination with certain other drugs, li&e fluorouracil 5'2H" and cyclophosphamide Cyto#an". Some of the most commonly used drug combinations for early breast cancer are: CA2 or 2AC": cyclophosphamide, do#orubicin Adriamycin", and 5'2H .AC: doceta#el .a#otere", do#orubicin Adriamycin", and cyclophosphamide AC O .: do#orubicin Adriamycin" and cyclophosphamide followed by paclita#el .a#ol" or doceta#el .a#otere".

2(C: O ., 5'2H, epirubicin, and cyclophosphamide followed by doceta#el .a#otere" or paclita#el .a#ol" .C: doceta#el .a#otere" and cyclophosphamide .C?: doceta#el, carboplatin, and trastuzumab ?erceptin" for ?(6!+neu positi$e tumors

Ather combinations that are less often used include C/2: cyclophosphamide Cyto#an", methotre#ate, and 5'fluorouracil fluorouracil, 5'2H" A O C/2: do#orubicin Adriamycin", followed by C/2 (C: epirubicin (llence" and cyclophosphamide AC: do#orubicin Adriamycin" and cyclophosphamide

.he targeted drug trastuzumab ?erceptin" may be gi$en along with chemo for early stage breast cancer when the cancer cells test positi$e for ?(6! this drug is discussed in the section about targeted therapy". /any other chemo drugs are useful in treating women with breast cancer, such as: 5latinum agents cisplatin, carboplatin" Ginorelbine 3a$elbine" Capecitabine Peloda" *iposomal do#orubicin 1o#il" Demcitabine Demzar" /ito#antrone I#abepilone I#empra" Albumin'bound paclita#el Abra#ane" (ribulin ?ala$en"

.argeted therapy drugs such as trastuzumab and lapatinib .y&erb" may be used with these chemo drugs for tumors that are ?(6!'positi$e these drugs are discussed in more detail in the Q.argeted therapy for breast cancerQ section". 1octors gi$e chemo in cycles, with each period of treatment followed by a rest period to gi$e the body time to reco$er from the effects of the drugs. Chemo begins on the first day of each cycle, but the schedule $aries depending on the drugs used. 2or e#ample, with some drugs, the chemo is gi$en only on the first day of the cycle. >ith others, it is gi$en e$ery day for 1; days, or wee&ly for ! wee&s. .hen, at the end of the cycle, the chemo schedule repeats to start the ne#t cycle. Cycles are most often ! or % wee&s long, but they $ary according to the specific drug or combination of drugs. Some drugs are gi$en more often. Ad-u$ant and neoad-u$ant chemo is often gi$en for a total time of % to < months, depending on the drugs that are used. .reatment may be longer for ad$anced breast cancer and is based on how well it is wor&ing and what side effects the patient has. 2ose-dense chemotherapy: 1octors ha$e found that gi$ing the cycles of certain chemo agents closer together can lower the chance that the cancer will come bac& and impro$e sur$i$al in some women. .his

usually means gi$ing the same chemo that may be gi$en e$ery % wee&s such as AC O .", but gi$ing it e$ery ! wee&s. A drug growth factor" to help boost the white blood cell count is gi$en after chemo to ma&e sure the white blood cell count returns to normal in time for the ne#t cycle. .his approach can be used for neoad-u$ant and ad-u$ant treatment. It can lead to more side effects and be harder to ta&e, so it isn0t for e$eryone.

>ossible side e%%ects

Chemo drugs wor& by attac&ing cells that are di$iding )uic&ly, which is why they wor& against cancer cells. But other cells in the body, li&e those in the bone marrow, the lining of the mouth and intestines, and the hair follicles, also di$ide )uic&ly. .hese cells are also li&ely to be affected by chemo, which can lead to side effects. Some women ha$e many side effectsF others may only ha$e few. Chemo side effects depend on the type of drugs, the amount ta&en, and the length of treatment. Some of the most common possible side effects include: ?air loss /outh sores *oss of appetite or increased appetite 3ausea and $omiting *ow 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" (asy bruising or bleeding from low blood platelet counts" 2atigue from low red blood cell counts and other reasons"

.hese side effects usually last a short time and go away after treatment is finished. ItNs important to tell your health care team if you ha$e any side effects, as there are often ways to lessen them. 2or e#ample, drugs can be gi$en to help pre$ent or reduce nausea and $omiting. Ather side effects are also possible. Some of these are more common with certain chemo drugs. Lour cancer care team will tell you about the possible side effects of the specific drugs you are getting. /enstrual changes: 2or younger women, changes in menstrual periods are a common side effect of chemo. 5remature menopause not ha$ing any more menstrual periods" and infertility not being able to become pregnant" may occur and may be permanent. Some chemo drugs are more li&ely to cause this than others. .he older a woman is when she recei$es chemotherapy, the more li&ely it is that she will become infertile or go through menopause as a result. >hen this happens, there is an increased ris& of bone loss and osteoporosis. .here are medicines that can treat or help pre$ent problems with bone loss.

($en if your periods ha$e stopped while you were on chemo, you may still be able to get pregnant. Detting pregnant while recei$ing chemo could lead to birth defects and interfere with treatment. .his is why it0s important that women who are pre'menopausal before treatment and are se#ually acti$e discuss using birth control with their doctor. 5atients who ha$e finished treatment li&e chemo" can safely go on to ha$e children, but itNs not safe to get pregnant while on treatment. If you are pregnant when you get breast cancer, you still can be treated. Certain chemo drugs can be gi$en safely during the last ! trimesters of pregnancy. .his is discussed in detail in the section, B.reatment of breast cancer during pregnancy.C If you thin& you might want to ha$e children after being treated for breast cancer, tal& with your doctor before you start treatment. Lou can read our document Fertility and Women With Cancer for more information. 3europathy: /any drugs used to treat breast cancer, including the ta#anes doceta#el and paclita#el", platinum agents carboplatin, cisplatin", $inorelbine, erubulin, and i#abepilone, can damage ner$es outside of the brain and spinal cord. .his can sometimes lead to symptoms mainly in the hands and feet" li&e numbness, pain, burning or tingling sensations, sensiti$ity to cold or heat, or wea&ness. In most cases this goes away once treatment is stopped, but it might last a long time in some women. 3europathy is discussed in more detail in our document, Peripheral Neuropathy Caused By Chemotherapy. Heart damage: 1o#orubicin, epirubicin, and some other drugs may cause permanent heart damage calledcardiomyopathy". .he ris& of this occurring depends on how much of the drug is gi$en, and is highest if the drug is used for a long time or in high doses. 1octors watch closely for this side effect. /ost doctors chec& the patient0s heart function with a test li&e a /HDA or an echocardiogram before starting one of these drugs. .hey 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 patients, heart damage ta&es a long time to de$elop. Signs might not appear until months or years after treatment stops. ?eart damage from these drugs happens more often if the targeted therapy drug trastuzumab is used as well, so doctors are more cautious when these drugs are used together. Hand-%oot syndrome: Certain chemo drugs, such as capecitabine and liposomal do#orubicin, can irritate the palms of the hands and the soles of the feet. .his is called hand-foot syndrome. (arly symptoms include numbness, tingling, and redness. If it gets worse, the hands and feet can become swollen and uncomfortable or e$en painful. .he s&in may blister, leading to peeling of the s&in or e$en open sores. .here is no specific treatment, although some creams may help. .hese symptoms gradually get better when the drug is stopped or the dose is decreased. .he best way to pre$ent se$ere hand'foot syndrome is to tell your doctor when early symptoms come up, so that the drug dose can be changed. .his syndrome can also occur when the drug 5'2H is gi$en as an IG infusion o$er se$eral days this is not commonly gi$en to treat breast cancer". Chemo brain: Another possible side effect of chemo is Qchemo brain.Q /any women who are treated for breast cancer report a slight decrease in mental functioning. .hey may ha$e some problems with concentration and memory, which may last a long time. Although many women ha$e lin&ed 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 ha$e found chemo brain to be a side effect of treatment, the symptoms most often go away in a few years. 2or more information, see our document, Chemo brain. Increased ris: o% leu:emia: Gery rarely, certain chemo drugs can permanently damage the bone marrow, leading to a disease called myelodysplastic syndrome or e$en acute myeloid leu&emia, a life' threatening cancer of white blood cells. >hen this happens it is usually within 14 years after treatment. In most women, the benefits of chemo in pre$enting breast cancer from coming bac& or in e#tending life are li&ely to far e#ceed the ris& of this rare but serious complication. 0eeling unwell or tired: /any women do not feel as healthy after recei$ing chemo as they did before. .here is often a residual feeling of body pain or achiness and a mild loss of physical functioning. .hese may be $ery subtle changes that are only re$ealed by closely )uestioning women who ha$e undergone chemo. 2atigue is another common but often o$erloo&ed" problem for women who ha$e recei$ed chemo. .his may last up to se$eral years. It can often be helped, so it is important to let your doctor or nurse &now about it. 2or more information on what you can do about fatigue, see our document, Fatigue in People with Cancer. (#ercise, naps, and conser$ing energy may be recommended. If there are sleep problems, they can be treated. Sometimes there is depression, which may be helped by counseling and+or medicines. 2or more information about chemotherapy, see our document, Understanding Chemotherapy ! "uide for Patients and Families. *ast /edical 6e$iew: 49+11+!41% *ast 6e$ised: 1!+%1+!41%