Benefits of MHT but Not Indications For Use
• Osteoporosis. MHT is effective and appropriate for the prevention of osteoporosis-related fractures in at-risk women age <60 or within 10 years after menopause.
• Coronary heart disease. Findings depend on the kind of MHT used.
– Estrogen-alone (ET) may decrease coronary heart disease and all-cause mortality in women age <60 and within 10 years of menopause.
– Estrogen plus progestogen (HT) in this age group shows a similar trend for decreased mortality but no significant increase or decrease in coronary heart dis-ease has been found.
Risks of MHT
• The risk of venous thromboembolism (VTE) and ischemic stroke increases with oral
MHT but the absolute risk is rare age <60. Observational studies point to a lower risk with transdermaltherapy.
• The risk of breast cancer in women age >50 associated with MHT is a complexone. The increased risk of breast cancer is primarily associated with the addition of a progestogen to estrogen therapy (HT) and related to the duration of use. The risk of breast cancer attributable to HT is small and decreases after treatment is stopped.
Current safety data do not support the use of MHT in breast cancer survivors.
Administration of Menopausal Hormone Therapy (MHT)
• Uterus present or absent. Estrogen as a single systemic agent (ET) is appropriate inwomen after hysterectomy but additional progestogen (HT) is required in the pres-ence of a uterus.
• Individualized management. The option of MHT is an individual decision in termsof quality of life and health priorities as well as personal risk factors such as age, time since menopause and risk of venous thromboembolism, stroke, ischemic heart disease and breast cancer.
• Dose and duration. Dose and duration of MHT should be consistent with treatmentgoals and safety issues, and thus should be individualized.
• Bioidentical hormones. The use of custom-compounded bioidentical hormone therapyis not recommended.
Estrogen alternatives
SERMs. In patients with contraindications to estrogen-replacement therapy, SERMs can beused. These are medications with estrogen agonist effects in some tissues, and estrogen antago-nist effects on others. Although protective against the heart as well as bone, these medications do not have much effect on hot flashes and sweats.
• Tamoxifen (Nolvadex) is an SERM with endometrial and bone agonist effects, butbreast antagonist effects.
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• Raloxifene (Evista) has bone agonist effects, but endometrial antagonist effects.
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The Female Breast 13
NORMAL BREAST DEVELOPMENT
Embryology
Breasts begin developing in the embryo about 7 to 8 weeks after conception, consisting only of a thickening or ridge of tissue.
• From weeks 12 to 16, tiny groupings of cells begin to branch out, laying the founda-tion for future ducts and milk-producing glands. Other tissues develop into muscle cells that will form the nipple (the protruding point of the breast) and areola (the darkened tissue surrounding the nipple).
• In the later stages of pregnancy, maternal hormones cause fetal breast cells to organize into branching, tube-like structures, thus forming the milk ducts. In the final 8 weeks, lobules (milk-producing glands) mature and actually begin to secrete a liquid sub-stance called colostrum.
• In both female and male newborns, swellings underneath the nipples and areolae can easily be felt, and a clear liquid discharge (colostrum) can be seen.
Puberty
From infancy to just before puberty, there is no difference between female and male breasts.
• With the beginning of female puberty, however, the release of estrogen—at first alone, and then in combination with progesterone when the ovaries are functionally mature—causes the breasts to undergo dramatic changes that culminate in the fully mature form.
• This process, on average, takes 3 to 4 years and is usually complete by age 16.
Anatomy
The breast is made of lobes of glandular tissue with associated ducts for transfer of milk to the exterior and supportive fibrous and fatty tissue. On average, there are 15 to 20 lobes in each breast, arranged roughly in a wheel-spoke pattern emanating from the nipple area. The distri-bution of the lobes, however, is not even.
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• There is a preponderance of glandular tissue in the upper outer portion of the breast. This is responsible for the tenderness in this region that many women experience prior to their menstrual cycle.
• About 80–85% of normal breast tissue is fat during the reproductive years. The
15 to 20 lobes are further divided into lobules containing alveoli (small sac-like fea-tures) of secretory cells with smaller ducts that conduct milk to larger ducts and finally to a reservoir that lies just under the nipple. In the nonpregnant, nonlactating breast, the alveoli are small.
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Note
Refer to Chapter 1, for a discussion of Tanner Stages.
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USMLE Step 2 l Gynecology
• During pregnancy, the alveoli enlarge. During lactation, the cells secrete milk substances (proteins and lipids). With the release of oxytocin, the muscular cells surrounding the alveoli contract to express the milk during lactation.
• Ligaments called Cooper’s ligaments, which keep the breasts in their characteristic shape and position, support breast tissue. In the elderly or during pregnancy, these ligaments become loose or stretched, respectively, and the breasts sag.
• The lymphatic system drains excess fluid from the tissues of the breast into the axillary nodes. Lymph nodes along the pathway of drainage screen for foreign bodies such as bacteria or viruses.
(Parasternal) 
Internal thoracic 
nodes 
Subclavian nodes
Interpectoral nodes
Axillary nodes
Brachial nodes
Subscapular nodes
Pectoral nodes
Sagittal View of Breast
Subcutaneous fat
Suspensory ligaments
Gland lobules
Lactiferous duct
Lactiferous sinus
Figure II-13-1. Breast
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Chapter 13 l The Female Breast
Hormones
Reproductive hormones are important in the development of the breast in puberty and in lactation.
• Estrogen, released from the ovarian follicle, promotes the growth ducts.
• Progesterone, released from the corpus luteum, stimulates the development of milk-producing alveolar cells.
• Prolactin, released from the anterior pituitary gland, stimulates milk production.
• Oxytocin, released from the posterior pituitary in response to suckling, causes milkejection from the lactating breast.
Lactation
• The breasts become fully developed under the influence of estrogen, progesterone, and prolactin during pregnancy. Prolactin causes the production of milk, and oxyto-cin release (via the suckling reflex) causes the contraction of smooth-muscle cells inthe ducts to eject the milk from the nipple.
• The first secretion of the mammary gland after delivery is colostrum. It contains more protein and less fat than subsequent milk, and contains IgA antibodies that impart some passive immunity to the infant. Most of the time it takes 1 to 3 days after deliv-ery for milk production to reach appreciable levels.
• The expulsion of the placenta at delivery initiates milk production and causes the drop in circulating estrogens and progesterone. Estrogen antagonizes the positive effect of prolactin on milk production.
• The physical stimulation of suckling causes the release of oxytocin and stimulates prolactin secretion, causing more milk production.
BENIGN BREAST DISORDERS
Cystic Breast Mass
A 40-year-old menstruating woman had a 2-cm cystic breast mass confirmed by breast ultrasonography.
Diagnosis. Cyst aspiration and fine-needle aspiration are important components in the pre-liminary diagnosis of breast disorders. Fine-needle aspiration of a palpable macrocyst, the appropriate procedure for this patient, can be performed in an office setting. Interpretation of fine-needle aspiration requires the availability of a trained cytopathologist.
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Management. Preaspiration mammography should be obtained. If the cyst disappears and thecytology is benign, no further workup is required.
Note
Mammograms are discussed in detail in chapter 1.
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Fibrocystic Breast Changes
A 30-year-old woman experiences bilateral breast enlargement and tenderness, which fluctuates with her menstrual cycle. On physical examination the breast feels lumpy, and the patient indicates a sensitive area with a discrete 1.5-cm nodule, which she says is consistently painful. A fine-needle aspiration is performed, and clear fluid is withdrawn. Clinically the cysts resolved.
Diagnosis. Cyclic premenstrual mastalgia is often associated with fibrocystic changes of thebreast; a condition that is no longer considered a disease but a heterogeneous group of disor-ders. Breast discomfort may be accompanied by a palpable mass. Fine-needle aspiration can easily distinguish whether a mass is solid or cystic. The procedure requires no special skill other than stabilizing the mass so that needle aspiration can be done with precision. The goal of cyst aspiration is complete drainage of the cyst with collapse of the cyst wall.
Management
• Mass disappears. If the cyst fluid is clear, it may be discarded. If the cyst fluid is grosslybloody, it should be sent for cytologic examination to rule out the possibility of intracys-tic carcinoma. After aspiration, the affected area must be palpated to determine whether there is a residual mass. If there is no residual mass, the patient may be reexamined in 4–6 weeks for the reaccumulation of fluid. If fluid reaccumulates, it may be aspirated again.
• Mass persists. A mass that persists requires further workup. A persistent accumula-tion is managed by mammography and excision. Because changes such as hematoma related to aspiration may affect mammographic appearances, it is recommended that mammography not be performed until 2 weeks after aspiration. Definitive evaluation of a persistent mass requires excisional biopsy.
• Conservative. Ultrasonography is useful in distinguishing cysts from solid masses.
If ultrasonography has been performed before aspiration and had shown a cyst with distinct smooth contours, an alternative management plan would be conservative follow-up with serial ultrasound scans. If the cyst disappears on aspiration and the fluid is clear, no further workup is required.
Breast Fibroadenoma
A 25-year-old woman visits the gynecologist for routine annual examination. During the examination she has a palpable, rubbery breast mass, which has been present and stable for the past 2 years. The pathology report of fine-needle aspiration was consistent with fibroadenoma.
Diagnosis. Fibroadenomas are the most common breast tumors found in adolescence andyoung women. In approximately 15% of patients they occur as multiple lesions. Clinically, fibro-adenomas are discrete, smoothly contoured, rubbery, nontender, freely moveable masses. The most distinctive gross feature of fibroadenomas that allows them to be distinguished from other breast lumps is their mobility. Fibroadenomas arise from the epithelium and stroma of the ter-minal duct lobular unit, most frequently in the upper outer quadrant of the breast. An associa-tion of fibroadenomas with the development of breast cancer has not been well established. Any associated increases in breast cancer risk depends on the presence of proliferative changes in the fibroadenoma itself or in the surrounding breast, and on a family history of breast carcinoma.
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Although cysts and fibroadenomas may be indistinguishable on palpation, ultrasound examination easily distinguishes cystic from solid lesions. On fine-needle aspiration, cysts typically collapse, whereas samples from a fibroadenoma present a characteristic combination of epithelial and stromal elements.
Management
• Conservative. Some clinicians advocate conservative management of fibroadenomas,especially in young women, because they can be diagnosed by ultrasonography and core-needle biopsy or fine-needle aspiration with a high degree of confidence, and in some cases they will resolve. A survey of patient preferences, however, has revealed
that many women choose excisional biopsy even when they are assured that the lesion is benign by fine-needle aspiration.
• Excision. Typically, the lesion is “shelled out” with a surrounding thin rim of breasttissue to avoid the necessity of reexcision in the rare instances when the tumor proves to be a phyllodes tumor. This is a mixed epithelial and stromal tumor that has benign, borderline, and malignant variants. The biology of the phyllodes tumor is determined by its stromal elements; in its fully malignant form, it behaves as a sarcoma.
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