BREAST DISEASES

Christiana P. Calagui-Damaso, M.D. FPSMS ANATOMY Breastsarelarge, modified sebaceous glands contained within the superficial fascia of the anterior chest wall Axillary tail of Spence A lateral projection of glandular tissue extends from the upper, outer portion of the breast toward the axilla 200 to 300g average weight of the adult breast during the menstruating years mature breast consists of approximately 20% glandular tissue and 80% fat and connective tissue The periphery of breast tissue is predominantly fat, and the central area contains more glandular tissue glandular portion of the breast is comprised of 12 to 15 independent ductal systems that each drain about 40 lobules Each lobule consists of 10 to 100 milk-producing acini that drain into small terminal ducts Terminal ducts drain into larger collecting ducts that merge into even larger ducts, which exhibit a saccular dilation just below the nipple called a lactiferous sinus 12 to 20 lobes arranged in radial fashion from the nipple Each lobe is triangular and has one central excretory duct that opens to the exterior at the nipple Milk originates in the secretory cells of the alveoli It is subsequently transported by the branching collecting ducts of the lobules into the lactiferous sinuses and terminally into the excretory ducts of each respective lobe of the breast Lobules

10 and 100, in each lobe of the breast ductal tissue surrounded by fibrous tissue Terminal ductules (TD) surround the central ductule (ID) EF, extralobularfibrocollagenous tissue

Montgomery glands are accessory glands located around the periphery of the areola Because they are structurally intermediate between true mammary and sebaceous glands, they can secrete milk Fibrous septa, Cooper's ligaments, extend from the skin to the underlying pectoralis fascia They are believed to offer support to the breast Invasion of these ligaments by malignant cells produces skin retraction, which is a sign of advanced breast carcinoma lymphatic distribution 75% of the lymphatic drainage goes to regional nodes in the axilla o axilla contains 30 and 60 nodes o axillary lymph nodes include the pectoral (chest), subscapular (under the scapula), and humeral (humerus-bone area) lymph-node groups, which drain to the central axillary lymph nodes and to the apical axillary lymph nodes Page 1

GYNECOLOGY BREAST DISEASES

25% of the lymph travels to the parasternal nodes (beside the sternum bone), to the other breast, and to the abdominal lymph nodes o Mediastinum intercostal glands subpectoral and subdiaphragmatic areas

Lymph drainage usually flows toward the most adjacent group of nodes This represents the basis for sentinel node mapping in breast cancer breast cancer spreads in an orderly fashion within the axillary lymph node basin based on the anatomic relationship between the primary tumor and its associated regional (sentinel) nodes

Development and Physiology Fetal development the primordial breast arises from the basal layer of the epidermis Before puberty the breast is a rudimentary bud comprised of a few branching ducts capped with alveolar buds, end buds, or small lobules At puberty - between the ages of 10 and 13 years ovarian estrogen and progesterone cooperate to direct organized communication between breast epithelial cells and mesenchymal cells, resulting in extensive branching of the ductal system and development of lobules Final differentiation of the breast is mediated by progesterone and prolactin and is not completed until the first full-term pregnancy Reproductive years - terminal ducts near the acini and the acini themselves are most sensitive to ovarian hormones and prolactin Luteal phase of the menstrual cycle Breast epithelial cells proliferate when estrogen and progesterone levels are increased, and then undergo programmed cell death at the end of the luteal phase, when levels of these hormones decline This effect is mediated by paracrine signaling induced by estrogen receptor activation and is associated with an increase in the water content of the extracellular matrix o This is often recognized as breast fullness and tenderness the week preceding menses o Premenstrual breast symptoms are produced by an increase in blood flow, vascular engorgement, and water retention o 25 to 30 mL - average increase in volume of the premenstrual breasts Follicular phase there is parenchymal proliferation of the ducts During the luteal phase there is dilation of the ductal system and differentiation of the alveolar cells into secretory cells Menstruation begins there is a regression of cellular activity in the alveoli and the ducts become smaller At menopause ovarian estrogen production ceases breast lobules involute, and the collagenous stroma is replaced by fat Because estrogen receptor expression is negatively regulated by estrogen, there is an increase in estrogen receptor expression after menopause

GYNECOLOGY BREAST DISEASES

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Breast Anomalies 1% to 2% of women of European descent and 5% to 6% of Asian women Accessory breasts or nipples o can occur along the breast or milk lines, which run from the axilla to the groin Supernumerary nipples (polythelia) or breasts (polymastia Massive hypertrophy of the breasts at puberty (virginal hypertrophy) rare occurrence that has a deeply disturbing effect on a teenager's self-image

EVALUATION OF BREAST DISEASES Detection 1. History Evaluation of a new breast symptom begins with assessment of symptoms based on a thorough clinical history Include questions regarding current symptoms, duration of the condition, fluctuation of the signs and symptoms, and factors that aggravate or relieve the symptom Assessment of breast problems should focus on the following points: Nipple discharge o Characteristics of discharge (spontaneous or nonspontaneous, appearance, unilateral or bilateral, single or multiple duct involvement) Breast mass (size and change in size, density, or texture) Breast pain (cyclic versus continuous) Association of symptoms with menstrual cycle Change in breast shape, size, or texture Previous breast biopsies Patient should be questioned about the following risk factors for breast cancer o Sex o Increasing age (approximately 50% of breast cancers occurafter age 65) o Age of menarche less than 12 years o Nulliparity or first pregnancy at greater than 30 years of age o Late menopause (older than 55 years of age) o Family history of breast cancer (especially premenopausal or bilateral disease) o Number of first-degree relatives with breast cancer and their ages when diagnosed o Family history of male breast cancer o Inherited conditions associated with a high risk for breast cancer, including BRCA1 and BRCA2 genes, Li-Fraumeni syndrome, Cowden's disease, ataxia telangiectasia syndrome, and PeutzJeghers syndrome o Other malignancies (ovary, colon, and prostate) o Pathology of previous breast biopsy showing atypia or lobular or ductal carcinoma in situ o Hormone therapy o Alcohol consumption o Postmenopausal weight gain o Personal history of breast cancer Breast cancer risk can be determined by the Gail Risk assessment model calculates risk based on patient race, age, age of menarche, age of first live birth, number of firstdegree relatives with breast cancer, number of previous breast biopsies, and presence of atypia on the biopsy

GYNECOLOGY BREAST DISEASES

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2.

Physical Examination Breast tumors, particularly cancerous ones, usually are asymptomatic and are discovered only by physical examination or screening mammography premenstrual phase - most women have increased innocuous nodularity and mild engorgement of the breast a. Inspection performed initially while the patient is seated comfortably with her arms relaxed at her sides Pay attention to the following signs for symmetry contour edema Discharge or secretions alterations of the nipple o retraction o eczema on one side skin modifications or appearance o redness or erythema o retraction of the skin o bulge of the breast o orange skin o Skin dimpling

Secretion

Tumor infiltrating the skin

Retraction of skin

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Inflammation /Redness/Erythema

Bulge of the breast

eczema on one side

Retraction of nipple

b. Palpation While the patient is seated, each breast should be palpated methodically palpate the breast in enlarging concentric circles until the entire breast has been covered Palpation should use the pads of the first three fingers placed together, exerting firm but gentle pressure Pendulous breast can be palpated by placing one hand between the breast and the chest wall and gently palpating the breast between both examining hands. The axillary and supraclavicular areas should be palpated for enlarged lymph nodes The entire axilla, the upper outer quadrant of the breast, and the axillary tail of Spence are palpated for possible masses PLATEAU SIGN retraction of the skin is invisible unless you move or shift the skin between the fingers of both hands While the patient is supine with one arm over her head, the ipsilateral breast is again methodically palpated from the clavicle to the costal margin If the breast is large o a pillow or towel should be placed beneath the scapula to elevate the side being examined o otherwise, the breast tends to fall to the side, making palpation of the lateral hemisphere more difficult Major features to be identified Temperature texture and thickness of skin Page 5

GYNECOLOGY BREAST DISEASES

generalized or focal tenderness Nodularity density asymmetry dominant masses nipple discharge mobility Premenopausal patients nodular breast parenchyma Breast cancer mass nontender, firm mass with irregular margins A cancerous mass feels distinctly different from the surrounding nodularity A malignant mass may be fixed to the skin or to the underlying fascia

Breast Self-examination Increases breast health awareness It helps promote early detection of cancer and may improve the survival rates for patients with breast carcinoma Most breast cancers are detected by women themselves (48%), followed by breast imaging (41%), and by physician clinical examination in only 11% Essential components of breast examination Positions Palpation Pads of fingers for palpation Pressure Perimeter Pattern of search Patient education It is helpful for all women to examine their breasts at the same time each month to develop a routine Premenopausal women should examine their breasts monthly 7 to 10 days after the onset of the menstrual cycle For postmenopausal women selection of a specific calendar date is a helpful way to remember to perform a monthly BSE Use the pads of her second, third, and fourth fingers to palpate the contralateral breast Using the pads of her fingers, in a massaging motion with firm pressure, she should examine the entire breast and surrounding chest wall in a systematic fashion One of the easier techniques to follow is to palpate the breasts in a clockwise fashion beginning at the nipple and gradually circumscribing larger circles

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3.

Breast Imaging a. Mammography screen-film mammography best method for imaging of the breast Advantages of digital mammography lower radiation exposure ability to manipulate a computerized image for optimal viewing access to distance consultations through telemammography Slow-growing breast cancers can be identified by mammography at least 2 years before the mass reaches a size detectable by palpation Mammography is the only reproducible method of detecting nonpalpable breast cancer Most practical method of detecting breast carcinoma at an early and highly curable stage, ideally discovering an occult cancer (<5 mm in diameter) Compression of the breast is necessary to obtain good images, and patients should be forewarned that breast compression is uncomfortable Clinical advantages of discovering breast carcinoma during its earliest stage higher percentage of localized disease lower incidence of positive regional nodes reduced mortality 85% 5-year survival rate for women whose breast cancer is believed to be localized to the breast with negative axillary nodes 53% the 5-year survival rate when axillary nodes are positive 74% Ten-year survival statistics in women with negative nodes 39% Ten-year survival statistics in women with positive nodes Breast carcinoma must develop neovascularization to grow beyond 12 mm in diameter Average breast carcinoma grows for 3 years, to enlarge from 1 mm to 1 cm Screening mammography reduces breast cancer mortality by approximately 33% in women 50 to 70 years of age Indications for Mammography To screen, at regular intervals, women who are at high risk for developing breast cancer To evaluate a questionable or ill-defined breast mass or other suspicious change in the breast that is detected by clinical breast examination To establish a baseline breast mammogram and reevaluate patients at yearly intervals to diagnose a potentially curable breast cancer before it has been diagnosed clin To search for occult breast cancer in a patient with metastatic disease in axillary nodes or elsewhere from an unknown primary origin To screen for unsuspected cancer before cosmetic operations or biopsy of a mass To monitor breast cancer patients who have been treated with a breast-conserving surgery and radiation. Mammographic Abnormalities includes a mass (solid versus cystic) microcalcifications (benign, indeterminate, suspicious) asymmetric density architectural distortion appearance of a new density Eight morphologic categories of mammographic abnormalities Calcification distribution Number of calcifications Description of calcifications Page 7

GYNECOLOGY BREAST DISEASES

Mass margin Shape of mass Density of mass Associated findings Special cases Malignancy clusters of fine calcifications spiculations poorly defined multinodular masses with irregular contours Mammograhic Screening Recommendaions of the American Cancer Society Mammograhic screening at age 40 o 24% reduction in mortality in screened populations For women in their 20s and 30s o clinical breast examination is suggested at least every 3 years, and preferably annually For women older than age 40 years, annual clinical breast examination For older women, recommendations for mammographic screening may be individualized based on the presence of any comorbidities Recommendaions of the American Geriatrics Society annual or at least biennial mammography for women up to age 75 years after 75 years, every 2 to 3 years if the woman has a life expectancy of more than 4 years For high-risk women, consideration can be given to earlier initiation of screening (5 to 10 years earlier than the age of the index case) and shorter intervals between screening

Normal mammogram

Breast Tumor

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b. Digital Radiography X-ray photons are detected after passing through the breast tissue and the radiographic image is recorded electronically in a digital format and stored in a computer Advantages compared with conventional mammography Image acquisition, display, and storage are much faster image manipulation through adjustments in contrast, brightness, and electronic magnification of selected regions enables radiologists to obtain superior views Helpful in screening women with very dense breasts and breast implants Disadvantages high cost of the equipment the limited image storage capacity the reduced spatial resolution due in part to inadequate resolution of current monitors c. Computed Tomography Has limited value when compared with mammography because of higher radiation dose and longer study times Excellent for studying the most medial and lateral aspects of the breast It is sometimes used for preoperative wire location of a mass that is difficult to localize by mammography

d. Magnetic Resonance Imaging Not be used in screening because of higher cost but as a diagnostic test Proven effective in detecting new tumors in patients with previous lumpectomy because it can accurately distinguish between scar tissue and cancerous lesions Indications Stage tumor to rule out multicentric disease Differentiate postoperative scar from recurrence after breast-conserving surgery Find a lesion seen in only one view of mammogram Evaluate positive axillary nodes in the presence of negative mammogram and clinical breast examination results Rule out silicone implant rupture Assess focal assymetry e. Ultrasonography complementary procedure to other imaging techniques in the diagnosis of breast disease, particularly in differentiating cystic from solid masses It should not be used as a screening test except for women with very dense breasts who cannot be adequately screened with mammography Advantages of ultrasound ability to produce images of breast tissue on multiple occasions without harmful effects It is most useful in evaluating solitary masses greater than 1 cm in diameter greatest limitation of ultrasonography The limited spatial resolution Microcalcifications are not visualized because resolution of less than 2 mm is difficult with ultrasound Indications for breast ultrasonography Characterization: o Palpable abnormality o Ambiguous mammographic findings o Silicone leak o Mass in woman younger than 30 years, lactating, or pregnant Guidance for interventional procedures o guide for needle aspiration, needle core biopsy, and in localization procedures Page 9

GYNECOLOGY BREAST DISEASES

also used to localize tumorsintraoperatively without a guide wire with excellent success rates Possible role for additional imaging in high-risk individuals Differentiate a cystic breast mass from a solid mass o most important use of ultrasound o 96% to 100% accuracy rate

f.

Mammoscintigraphy (Scintimammography) Radionuclide imaging test for the detection of breast cancer High diagnostic accuracy for the detection of breast cancer in all women, including women who may be unsuitable for conventional mammography

Breast Tissue Evaluation: Histology and Cytology 30% of lesions suspected to be cancer prove on biopsy to be benign 15% of lesions believed to be benign prove to be malignant Dominant masses or suspicious nonpalpable mammographic findings must be evaluated by biopsy An apparently fibrocystic lesion that does not completely resolve within several menstrual cycles should be sampled for biopsy Any mass in a postmenopausal woman who is not taking estrogen therapy should be presumed to be malignant

Algorithm for management of breast masses in postmenopausal women

Palpable mass Not clinically malignant Not obviously malignant

Mammography

Mammography

FNAC or Core Needle Biopsy

Preoperative evaluation and counselling

Excisional Biopsy Definitive Procedure

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Algorithm for management of breast masses in premenopausal women

Palpable mass Not clinically malignant Clinically malignant

Mammogram Ultrasound cystic Solid but not suggestive of malignancy excision aspirate Excise or re-examine after next menses or 1-2 months Appears malignant

mammogram

FNAC or Core Needle Biopsy

Preoperative evaluation and counselling

Definitive procedure

Nonbody fluid

persistence

resolution

resolves

excision

Routine follow up

reexamine

recurrence

No recurrence

excision

Routine follow up

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1.

Fine-needle Aspiration The color of the fluid obtained via aspiration varies from clear to grossly bloody A biopsy should be performed on cysts that recur within 2 weeks or that necessitate more than one repeat aspiration sensitivity of FNA for palpable masses is approximately 90% false-negative rate that varies from 0.7% to 22% Biopsy Core Needle or Open Biopsy Indications for tissue biopsy bloody discharge from the nipple a persistent three-dimensional mass suggestive mammography Nipple retraction or elevation skin changes, such as erythema, induration, or edema

2.

BENIGN BREAST CONDITIONS Three life cycles reflect different reproductive phases in a woman's life and are associated with unique breast manifestations During the early reproductive period (15-25 years), lobule and stromal formation occurs o fibroadenoma (mass) and juvenile hypertrophy (excessive breast development) During the mature reproductive period (25-40 years), cyclic hormonal changes affect glandular tissue and stroma o cyclic mastalgia and generalized nodularity involution of lobules and ducts or turnover of epithelia, which occurs during ages 35 to 55 years o macrocysts (lumps) o sclerosing lesions (mammographic abnormalities) o Those associated with ductal involution - duct dilation (nipple discharge) and periductal fibrosis (nipple retraction) o those with epithelial turnover are mild hyperplasia (pathologic description) 1. Fibrocystic Change most common lesion of the breast refers to a histologic picture of fibrosis, cyst formation, and epithelial hyperplasia Cysts arise from the breast lobules and are an aberration of normal breast involution common in women ages of 20 and 50 (35 to 55 years of age) but rare in postmenopausal women not taking hormone therapy it is present bilaterally, increased in the perimenopausal age group, and responsive to endocrine therapy believed to be an exaggeration of the normal physiologic response of breast tissue to the cyclic levels of ovarian hormones imbalance of the ratio of estrogen to progesterone secondary to increased daily prolactin production Women with fibrocystic changes have enhanced prolactin production in response to thyroid-releasing hormone Signs and Symptoms - more prevalent during the premen-strual phase of the cycle cyclic bilateral breast pain classic symptom pain is most frequently located in the upper, outer quadrants of the breasts. Often the pain radiates to the shoulders and upper arms increased engorgement and density of the breasts excessive nodularity rapid change and fluctuation in the size of cystic areas increased tenderness Page 12

GYNECOLOGY BREAST DISEASES

occasionally spontaneous nipple discharge Differential diagnosis of breast pain Referred pain from a dorsal radiculitis Inflammation of the costal chondral junction (Tietze's syndrome) Physical Examination Excessive nodularity of fibrocystic changes is similar to palpating the surface of a plateful of peas Multiple solid areas are described as ill-defined thicknesses or areas of palpable lumpiness that are rubbery in consistency and may seem more two-dimensional than the threedimensional mass usually associated with a carcinoma The larger cysts have a consistency similar to a balloon filled with water Clinical Stages a. mazoplasia (mastoplasia) first stage occurs in women in their 20s Breast pain is noted primarily in the upper, outer quadrants of the breast The indurated axillary tail is in the most tender area of the breast There is intense proliferation of the stroma b. Adenosis second stage women in their 30s breast pain and tenderness are premenstrual but less severe Multiple small breast nodules vary from 2 to 10 mm in diameter marked proliferation and hyperplasia of ducts, ductules, and alveolar cells c. Cysticphase - third stage women in their 40s There is no severe breast pain unless a cyst increases rapidly in size woman experiences a sudden pain with point tenderness and discovers a lump Cysts are tender to palpation and vary from microscopic to 5 cm in diameter fluid aspirated from a large cyst is straw-colored, dark brown, or green Diagnostic Tests Characteristic findings on ultrasonography o Mass with thin walls o Smooth round shape o Absence of internal echoes o Posterior acoustic enhancement If these imaging criteria are not met, a tissue diagnosis of the mass usually requires a FNA, FNAC, or EB Fine needle aspiration Benign cyst fluid - straw colored to dark green to brownish Fibrocystic change is not associated with an increased risk of breast cancer unless there is histologic evidence of epithelial proliferative changes, with or without atypia If there is a persistent dominant mass or any uncertainty in the examination, a biopsy of the area should be performed to rule out a malignancy Management patient wearing a support bra, which provides adequate support for the breasts both night and day Diuretics during the premenstrual phase occasionally relieve breast discomfort Oral contraceptives or supplemental progestins administered during the secretory phase of the cycle Danazol drug of choice for severe symptoms 100, 200, and 400 mg daily continuously for 46 months should not continue more than 6 months because side effects are common Bromocriptine or Tamoxifen Patients who do not respond to danazol Page 13

GYNECOLOGY BREAST DISEASES

Bromocriptine - an inhibitor of prolactin given continuously of 5 mg daily Tamoxifen - a synthetic antiestrogen 70% relief of breast symptoms when prescribed for fibrocystic changes

2.

Fibroadenomas firm, rubbery, freely mobile, solid, usually solitary breast masses second most common type of benign breast disease adolescents and women in their 20s Usually discovered accidentally while bathing Do not change in size with the menstrual cycle, and they do not produce breast pain or tenderness 30% will disappear and 10% to 12% become smaller average fibroadenoma is 2.5 cm in diameter responsive to estrogen stimulation not associated with an increased risk for breast cancer Sonography - differentiating a solid from a cystic mass FNAB Open biopsy or surgical removal CystosarcomaPhyllodes fibroepithelial breast tumors hypercellularity of the connective tissue rare - represent only 2.5% of fibroepithelialtumors and 1% of breast malignancies They are the most frequent breast sarcoma Rapidly growing tumors Most common in the fifth decade of life Rarely bilateral and usually appear as isolated masses that are difficult to distinguish clinically from a fibroadenoma Patients often relate a long history of a previously stable nodule that suddenly increases in size Reported sizes range from 1.0 to 50 cm Factors that are considered in recommending excision include older age new mass in a well-screened individual rapid growth size greater than 2.5 to 3 cm suspicious FNAC or CB mammographic or ultrasonographic features that demonstrate lobulation and intramural cysts Treatment - wide local excision, attempting to obtain a 1- to 2-cm margin Prognosis benign phyllodestumors can recur locally in up to 10% of patients Malignant phyllodestumors tend to recur locally and occasionally may metastasize to the lung, although brain, pelvic, and bone metastases also may occur Borderline tumor Malignanttumor

3.

GYNECOLOGY BREAST DISEASES

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4.

Intraductal Papilloma spontaneous bloody discharge from one nipple - classical symptom discharge from the nipple is spontaneous and intermittent watery, serous, or serosanguineous When the discharge comes from a single duct, the differential diagnosis involves both intraductal papilloma and carcinoma If multiple ducts are involved, the diagnosis of carcinoma is more likely perimenopausal age group 75% of intraductalpapillomas are located beneath the areola difficult to palpate because they are small and soft Treatment - excisional biopsy of the involved duct and a small amount of surrounding tissue Nipple Discharge complaint of 10% to 15% of women with benign breast disease spontaneous nipple discharge is infrequently found to be associated with carcinoma, ranging from 4% to 10% Nonneoplastic processes galactorrhea physiologic changes resulting from mechanical manipulation parous condition periductal mastitis subareolar abscess fibrocystic change mammary duct ectasia Neoplastic causes in nonlactating women solitary intraductal papilloma carcinoma papillomatosis squamous metaplasia adenosis Characteristics of the discharge to be evaluated Nature of discharge (serous, bloody, or milky) Association with a mass Unilateral or bilateral Single or multiple ducts Discharge that is spontaneous (persistent or intermittent) or expressed by pressure at a single site or on entire breast Relation to menses Premenopausal or postmenopausal Hormonal medication (contraceptive pills or estrogen) Chronic unilateral nipple discharge, especially if it is bloody, is an indication for resection of the involved ducts Treatment surgical excision o periareolar incision adjacent to the trigger point, the pressure point that elicits nipple discharge Fat Necrosis Rare but clinically important because it produces a mass, often accompanied by skin or nipple retraction, which is indistinguishable from carcinoma Page 15

5.

6.

GYNECOLOGY BREAST DISEASES

 7.

firm, tender, indurated, ill-defined mass that may have an area of surrounding ecchymosis Sometimes the area of fat necrosis liquefies and becomes cystic in consistency needle-core excisional biopsy of the entire mass to rule out carcinoma

Breast Abscess Lactational Abscesses Staphylococcus aureus mastitis is diagnosed, manual pressure, antibiotics, and continued breastfeeding are recommended dicloxacillin 250 mg four times daily, or oxacillin, 500 mg four times daily for 7 to 10 days If the lesion progresses to a localized mass with local and systemic signs of infection, an abscess is present It should be drained, and breastfeeding should be discontinued Nonlactational Abscess Staphylococcus epidermidis Staphylococcus aureus Proteus mirabilis Pseudomonas aeruginosa sterile abscess If these infections recur after multiple aspirations, incision and drainage followed by excision of the involved lactiferous duct or ducts at the base of the nipple may be necessary during a quiescent interval

BREAST CARCINOMA Epidemiology Established and Probable Risk Factors for Breast Cancer Risk Factor Family history of breast cancer - 5% to 10% BRCA1 (chromosome 17q21) and BRCA2 Comparison Category No first-degree relatives affected Risk Category Mother affected before the age of 60 Typical Relative Risk 2.0

Mother affected 1.4 after the age of 60 Two first-degree relatives affected Age at menarche - There is no clear association between the risk of breast cancer and menstrual irregularity and the duration of menses 16 yr 11 yr 12 yr 13 yr 14 yr 15 yr 46 1.3 1.3 1.3 1.3 1.1

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Age at birth of 1st child If a woman's first term birth occurs before age 20, she has 50% less risk than a nulliparous woman. If the first full-term pregnancy occurs after age 35, the risk is 1.5 times greater than for women who have their first baby before age 26 It was believed that nursing an infant offered a protective effect for the future development of breast neoplasia related to the intensity and duration of exposure to unopposed endogenous estrogen

Before 20 yr

2024 yr 2529 yr 30 yr

1.3 1.6 1.9

Nulliparous

1.9

Age at menopause - After menopause the incidence of breast 4554 yr carcinoma increases directly with a woman's age -twofold increased risk for women who menstruated for 40 years or longer - Bilateral oophorectomy before age 35, without hormonal replacement, reduces the risk of breast carcinoma by 70% Benign breast disease No biopsy or aspiration

After 55 yr Before 45 yr Oophorectomy before 35 yr

1.5 0.7 0.4

Any benign disease Proliferation only

1.5 2.0

Atypical hyperplasia 4.0 Radiation - Ionizing radiation is a definite risk factor because of the long-accepted relationship between radiation and malignant transformation No special exposure Atomic bomb (100 rad) Repeated fluoroscopy 10th percentile 90th percentile: Age, 3049 yr Age, 50 yr Height 10th percentile 90th percentile: Age, 3049 yr Age, 50 yr Oral contraceptive use - no consensus on the association of exogenous estrogen administration Postmenopausal estrogen-replacement therapy - no consensus on the association of exogenous estrogen administration Never used Current use Past use Never used
[*] [*]

3.0 1.5 2.0

Obesity - increased amount of peripheral conversion of androstenedione to estrone and decreased levels of sex hormonebinding globulin

0.8 1.2

1.3 1.4 1.5 1.0

Current use all ages 1.4 Age, <55 yr Age, 5059 yr Age, 5059 yr 1.2 1.5 1.5 2.1 2.0

Past use Alcohol use

1.0 Nondrinker

Age, 60 yr 3 drinks/day

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Detection and Diagnosis use of screening tests in asymptomatic women at periodic intervals to discover breast malignancies Physical examination detects 10% to 20% of cancers not seen radiographically 10% to 50% of cancers detected mammographically are not palpable Breast cancer most commonly arises in the upper outer quadrant, where there is proportionally more breast tissue Masses are easier to palpate in older women with fatty breasts than in younger women with dense, nodular breasts When a dominant breast mass is identified, the presence of a carcinoma must be considered biopsy should be performed to establish a tissue diagnosis About 30% to 40% of lesions believed clinically to be malignant will be benign on histologic examination Prevention lifestyle modifications associated with good general health weight control, avoidance of smoking, decreased alcohol consumption, and exercise tamoxifen had a significant decrease in the incidence of contralateral breast cancers Surgical prophylaxis Classification classic sign solitary, solid, three-dimensional, dominant breast mass borders of the mass are usually indistinct, which makes it difficult to define precisely the size of the mass mass is not freely mobile Far-advanced local disease produces changes in the skin and nipples of the breast, includ-ing retraction, dimpling, induration, edema (peaud'orange), ulceration, and signs of inflammation

Simplified Classification of Breast Carcinoma Type of Carcinoma Ductal Carcinoma - in situ - infiltrating Lobular Carcinoma - In situ - Infiltrating - Inflammatory carcinoma - Paget's disease Percentage of All Cases Diagnosed 5 80 3 9 2 1

Intraductalcarcinomain situ the cellular abnormalities are limited to the ductal epithelium and have not penetrated the base membrane It is most commonly discovered in perimenopausal and postmenopausal women. not usually detected by palpation because the disease does not produce a definitive mass Mammography sometimes demonstrates the fine stippling of microcalcifications. The histologic diagnosis includes a heterogeneous group of tumors with varying malignant potential

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Lobular carcinoma in situ considered to be a marker for an increased breast cancer risk It does not have the same malignant potential as intraductal carcinoma in situ has a much greater tendency to be bilateral and to present as multifocal disease Infiltrating ductal carcinoma most common breast malignancy Histologically, nonuniform malignant epithelial cells of varying sizes and shapes infiltrate the surrounding tissue Infiltrating lobular carcinomas characterized by the uniformity of the small, round neoplastic cells the malignant epithelial cells infiltrate the stroma in a singlefile fashion tends to have a multicentric origin in the same breast and tends to involve both breasts more often than infiltrating ductal carcinoma Histologic subdivisions small cell round cell signet cell carcinomas Inflammatory carcinomas 2% of breast cancers initially appear to have acute inflammation of the breast with corresponding redness and edema recognized clinically as a rapidly growing, highly malignant carcinoma Infiltration of malignant cells into the lymphatics of the skin produces a clinical picture that simulates a skin infection Paget's disease less than 1% has an innocent appearance and looks like eczema or a dermatitis of the nipple erosion results from invasion of the nipple and surrounding areola by characteristic large cells with irregular nuclei, called Paget cells produced by an infiltrating ductal carcinoma that invades the epidermis has an excellent prognosis

Breast Cancer in Pregnancy complicates 1 in 3,000 pregnancies second most common malignancy seen in association with pregnancy Generalized recommendations for treatment cancers diagnosed during the first or second trimester of pregnancy have been treated with modified radical mastectomy. Sentinel node biopsy remains a controversial procedure in pregnancy Localized tumors found during the third trimester of pregnancy can be managed with breast conservation therapy, with radiation delayed until after delivery, or with modified radical mastectomy If the breast cancer is diagnosed during lactation, lactation should be suppressed and the cancer should be treated definitively Advanced, incurable cancer should be treated with palliative therapy

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Treatment of Breast Cancer four most important variables for treatment selection tumor'ssiz its inherent aggressiveness, as determined by the histology of the initial lesion the presence of positive nodes the receptor status of the tumor TNM system widely recognized staging system based on both clinical and pathologic criteria Surgical Therapy radical mastectomy o standard operation for carcinoma of the breast o designed to control local disease by an extensive en bloc removal of the breast and underlying pectoralis major and pectoralis minor muscles and complete axillary dissection o It is a cosmetically disfiguring operation, leaving a major deformity of the chest wall modified radical mastectomy removes the breast and only the fascia over the pectoralis major muscle. The pectoralis minor muscle may be removed to facilitate the axillary dissection Simple mastectomy o removal of the breast without underlying muscle tissue Stages I and II breast cancer o conservative surgery, which preserves the breast, followed by radiation therapy Medical Therapy Adjuvant systemic chemotherapy decreases the odds of dying from breast cancer during the first 10 years following diagnosis by approximately 25% Tamoxifen Medroxyprogesterone (Depo-Provera) Androgens danazol gonadotropin hormone-releasing hormone (GH-RH) agonists Combination therapy o paclitaxel Adriamycin cyclophosphamide o cyclophosphamide (C), methotrexate (M), and 5-fluorouracil (5-FU).

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Primary Tumor (T) TX T0 Tis T1 T1a T1b T1c T2 T3 T4 T4a T4b T4c T4d
[*]

Primary tumor cannot be assessed No evidence of primary tumor Carcinoma in situ. Intraductal carcinoma, lobular carcinoma in situ, or Paget's disease of the nipple with no tumor Tumor is 2.0 cm in greater dimension Tumor is 0.5 cm in greatest dimension Tumor is >0.5 cm but not more than 1.0 cm in greatest dimension Tumor is more than 1.0 cm but not more than 2.0 cm in greatest dimension Tumor is >2.0 cm but not more than 5.0 cm in greatest dimension Tumor is >5.0 cm in greatest dimension Tumor of any size with direct extension to chest wall or skin Extension to chest wall Edema (including peau d'orange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breast Both T4a and T4b above Inflammatory carcinoma

Regional Lymph Node Involvement (N) (Clinical) NX N0 N1 N2 N3 Regional lymph nodes cannot be assessed (e.g., previously removed) No regional lymph node metastasis Metastasis to movable ipsilateral axillary lymph node(s) Metastasis to ipsilateral axillary lymph node(s) fixed to one another or the other structures Metastasis to ipsilateral mammary lymph node(s)

Distant Metastasis (M) MX M0 M1 Presence of distant metastasis cannot be assessed No distant metastasis Distant metastasis (includes metastasis to ipsilateral supraclavicular lymph node[s])

Stage Grouping Stage 0 Stage I Stage IIa Tis T1 T0 T1 T2 Stage IIb T2 T3 Stage IIIa T0 T1 T2 T3 Stage IIIb T4 Any T Stage IV Any T N0 N0 N1 N1 N0 N1 N0 N2 N2 N2 N1, N2 Any N N3 Any N
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M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M1

GYNECOLOGY BREAST DISEASES

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GYNECOLOGY BREAST DISEASES

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