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General Principles in Older Adults
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The median age for the development of breast cancer is 61 years. The incidence of breast cancer increases with age and plateaus in the seventh decade. In 1973, 37% of breast cancer were diagnosed in women older than 65 years. Between 1996 and 2000 that number increased to 44.2% with 22.5% ≥75 years. The natural history of breast cancer in older populations is unique. When prognostic factors such as estrogen receptor (ER), histologic grade, ploidy, p5p3, epithelial growth factor receptor (EGFR), and human epidermal growth receptor 2 (HER2) status are assessed, it appears that tumors become less aggressive with advancing age. Despite this, 60% of breast cancer-related deaths involve women 65 years of age and older. The high mortality rate may be explained by several factors. First, breast cancer is a common disease in this age group, and patients often have life-threatening comorbid conditions. Second, physicians tend to treat older patients less aggressively than younger individuals.
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Primary Breast Cancer
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Treatment recommendations should be made on an individual basis, taking into consideration comorbid conditions and expectations of therapy. Whenever possible, patients should be encouraged to participate in clinical trials designed to assess how cancers can best be managed.
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Breast Conservation Therapy
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Although modified radical mastectomy and breast conservation therapy with lumpectomy and radiation share similar survival rates, older women are less likely to undergo breast conservation therapy. Possibly some women choose mastectomy because they find the 6–7 weeks of daily radiation treatments for breast conservation cumbersome. It has also been shown that physicians are less likely to offer breast conservation therapy to older women.
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Data suggest that, after surgical removal of the primary cancer, tamoxifen without radiation therapy may be adequate in select patients. However, by eliminating breast irradiation, ipsilateral breast cancer recurrences are more common and are generally treated by mastectomy for local control of the primary cancer. Despite the higher rate of “in-breast” recurrences, the survival for women treated with this less-aggressive approach is identical to that among women treated with conventional surgery and radiation therapy. Resection of the primary tumor and administration of tamoxifen may be appropriate for select women with small, ER+ breast cancers, and a finite life expectancy. Older women with a favorable long-term outlook should be treated as aggressively as younger women.
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For women with localized ER+ breast cancers, 5 years of adjuvant endocrine therapy decreases the recurrence rate and incidence of contralateral breast cancers. In older women on tamoxifen, the incidence of venous thromboemboli and uterine cancer is higher than in younger women; however, the benefits of adjuvant tamoxifen outweigh the risks. Adjuvant aromatase inhibitors (anastrozole, letrozole, and exemestane) are generally prescribed in postmenopausal women. When chemotherapy is indicated, the reduction in recurrence and survival advantage is identical to that observed in younger women. Less-toxic chemotherapy regimens are less effective than conventional chemotherapy.
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Although one must weigh comorbid conditions when making treatment recommendations, appropriately administered adjuvant therapy is cost-effective. In the absence of severe comorbidities, the guidelines for adjuvant therapy are identical to those used to treat younger women. Women with ER+, node-negative breast cancers should have the primary tumor submitted for the 21-gene, Oncotype Recurrence Score, which is helpful in identifying patients who will benefit from chemotherapy in addition to endocrine therapy. Chemotherapy should be considered for those women whose primary cancers are >1 cm and ER− or HER2-positive, and for those with multiple node involvement. The addition of the humanized monoclonal antibody trastuzumab (Herceptin) to conventional chemotherapy is associated with an improved survival and should be used despite a higher incidence of cardiac toxicity in woman older than age 65 years and in patients with hypertension.
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Because the majority of breast cancers are ER+, endocrine therapy is the mainstay of treatment for advanced breast cancers. The aromatase inhibitors have achieved a higher rate of tumor regression and a longer duration of efficacy and have replaced tamoxifen as first-line therapy for metastatic disease. In ER− disease and cancers that are hormone resistant, chemotherapy may provide effective palliation. Newer, less-toxic single agents such as oral capecitabine are as effective as combination chemotherapy. In women with newly diagnosed HER2-positive breast cancer, anti-HER2 therapy is added either to an aromatase inhibitor in hormone receptor-positive disease or to chemotherapy in hormone receptor-negative of hormone refractory disease. Combined anti-HER2 therapy with trastuzumab and pertuzumab with chemotherapy has been shown to further improve survival compared to trastuzumab and chemotherapy alone.
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A systematic review conducted by the U.S. Preventive Services Task Force (USPSTF) in 2009 led to recommendations for biennial film mammography for women ages 50–74 years; there was insufficient evidence to recommend screening mammography for women age 75 years and older. However, screening mammography decreases breast cancer mortality in women aged 70–79 and identifies early lesions in older women as effectively as in younger women. A single decision analysis and cost-effectiveness study of mammography in women age 70 years and older demonstrated that survival may be favorably affected by screening mammography. Given the heterogeneity of health, particularly in the older-than-75-years population, recommendations should be based on age and health status. For example, the American Geriatrics Society recommends screening mammography in women up to age 85 years, provided that their life expectancy is at least 4 years.