Porth's Essentials of Pathophysiology, 4e

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Genitourinary and Reproductive Function

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Proliferative Lesions with Atypia. Proliferative dis- ease with atypia includes atypical ductile hyperplasia and atypical lobular hyperplasia. 57 The hyperplasia is accompanied by replacement of the normal epithe- lial cells lining the ducts or lobules with atypical cells resembling those of carcinoma in situ. The basement membrane remains intact and, therefore, the cells can- not metastasize. There are two types of atypical hyperplasia: lobular and ductile. 57 Atypical ductile hyperplasia is recognized by its histologic resemblance to ductile carcinoma in situ (DCIS). Atypical lobular hyperplasia is defined by pro- liferation of cells identical to those of lobular carcinoma in situ (LCIS), but the cells do not fill or distend more than 50% of the acini within the lobule. Management of LCIS consists of excisional biopsy. Women with DCIS are at increased risk for developing invasive cancer or recurrence of the DCIS lesion. For this reason, DCIS is evaluated with core-needle biopsy (to be discussed) fol- lowed by surgical biopsy or excision. Women with both types of lesions require careful follow-up to prevent and detect the presence of invasive cancer. Breast Cancer Cancer of the breast is the most common female cancer. Although the breast cancer mortality rate has shown a slight decline, it is second only to lung cancer as a cause of cancer-related deaths in women. The decline in the breast cancer mortality is due to a number of factors, especially improvements in screening and treatment. Risk factors for breast cancer include increasing age, personal or family history of breast cancer (i.e., at highest risk are those with multiple affected first-order relatives), history of benign breast disease (i.e., primary “atypical” hyperplasia), and hormonal influences that promote breast maturation and may increase the chance of cell mutation (i.e., early menarche, late menopause, and no term pregnancies or first child after 30 years of age). Modifiable risk factors include obesity (particularly after menopause), physical inactivity, caffeine, moder- ate to heavy consumption of alcohol, cigarette smoking, and long-term use of postmenopausal hormone therapy (especially combined estrogen and progestin). 57 Most women with breast cancer have no identifiable risk factors. Approximately 12% of all breast cancers are heredi- tary. The probability of a hereditary etiology increases with multiple affected first-degree relatives, with women who are affected before 50 years of age, and those who have multiple cancers. 57 Mutations in two breast cancer susceptibility genes— BRCA1 on chro- mosome 17 and BRCA2 on chromosome 13—may account for most inherited forms of breast cancer (see Chapter 7). BRCA1 is known to be involved in tumor suppression. A woman with known mutations in BRCA1 has a lifetime risk of approximately 57% for breast cancer and approximately 40% for ovarian can- cer. BRCA2 is another susceptibility gene that elevates lifetime breast cancer risk to 49% and ovarian cancer risk to 18%. 59,60 Breast cancer risk reduction options

available to known carriers of BRCA1 and BRCA2 mutations include surveillance and surgery. Breast eval- uation using MRI, digital mammography, and breast ultrasound give the best sensitivity for detecting breast cancer. Prophylactic surgery, in the form of bilateral mastectomy, bilateral oophorectomy, or both, has been shown to decrease the risk of developing cancer. These controversial surgeries can have physical and psycho- logical side effects that warrant careful consideration before proceeding. Detection Cancer of the breast may manifest clinically as a mass, a puckering, nipple retraction, or unusual discharge. Many cancers are found by women themselves—some- times when only a thickening or subtle change in breast contour is noticed. The variety of symptoms and poten- tial for self-discovery underscore the need for all women to have an awareness of what their normal breast appearance and texture are like. Mammography is the only effective screening tech- nique for the early detection of clinically inapparent breast lesions. A generally slow-growing form of cancer, breast cancer may have been present for 2 to 9 years before it reaches 1 cm, the smallest mass normally detected by palpation. Mammography can disclose lesions as small as 1 mm and the clustering of calcifica- tions that may warrant biopsy to exclude cancer. In 2003, the American Cancer Society dropped its recommendation that all women perform regular, sys- tematic breast self-examination (BSE). Research has indi- cated that most women who discover their own cancer do so at times other than scheduled BSE. The American Cancer Society screening guidelines now place primary emphasis for breast cancer diagnosis on clinical breast examination (CBE) by a trained health professional and mammography, while encouraging women in the area of self-awarenenss. 21 Between the ages of 20 and 39 years, average risk women should undergo CBE every 3 years, and after age 40 years CBE should take place annually, ideally prior to the woman’s annual mammo- gram. 21 There is no specific upper age at which mam- mogram should be discontinued. Instead it is suggested that decision to stop mammogram screening should be individualized based on the potential risks and benefits. As long as the woman is in good health and would be a candidate for cancer treatment, it is recommended that she continue to be screened with mammography. 21 Diagnosis and Classification Procedures used in the diagnosis of breast cancer include physical examination, mammography, ultrasonography, percutaneousneedleaspiration,stereotacticneedlebiopsy (i.e., core biopsy), and excisional biopsy. Figure 40-19 illustrates the appearance of breast cancer on mam- mography. Breast cancer often manifests as a solitary, painless, firm, fixed lesion with poorly defined borders. It can be found anywhere in the breast but is most com- mon in the upper outer quadrant. Because of the vari- ability in presentation, any suspect change in breast tissue warrants further investigation. The diagnostic