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Adjuvant Treatment of Breast Cancer in the Elderly

Adjuvant Treatment of Breast Cancer in the Elderly

ABSTRACT: ABSTRACT: Breast cancer is the most common malignancy in women, and the incidence of breast cancer increases with increasing age until age 80. As the population continues to age, breast cancer in older women will become an increasing clinical challenge. A majority of breast cancer in older women is hormone receptor–positive, making hormonal therapy the mainstay of adjuvant treatment in this group. Chemotherapy clinical trials have largely excluded the elderly, and therefore limited data exists on the efficacy and tolerability of standard adjuvant chemotherapy in older women. Ongoing studies are addressing alternatives to standard adjuvant chemotherapy in this group. Emerging biologic instruments such as gene-expression profiling may be able to better identify patients who will gain benefit from adjuvant chemotherapy. Elderly patients are highly variable in their functional status, reserve capacity, and comorbidity, and better assessment tools are needed to evaluate these issues and predict which patients will tolerate cancer treatments. More work is needed to address the many challenges that affect the adjuvant treatment of breast cancer in older women.

Breast cancer is the most common life-threatening malignancy in women, and the second leading cancer killer of women, claiming the lives of over 40,000 American women annually.[1] Breast cancer incidence increases with advancing age until age 80, and the median age at diagnosis is 61.[2] The population, in America and worldwide, is aging due to improvements in health care and nutrition, and it is estimated that the number of Americans over the age of 65 will increase from 30 million in 2000 to over 71 million in 2030.[3] Given the relationship between age and breast cancer incidence, as the absolute number of women over age 65 (and even over 85) grows, breast cancer will be an increasingly common diagnosis.

More specifically, breast cancer in older women will become even more prevalent, and we must improve our understanding of how best to treat these women. This will require clinical trials focusing specifically on treatments in this age group and an improved understanding of the complex interactions between cancer biology, cancer therapy, normal physiologic changes of aging, comorbid illness, and functional status. The goal of such research should be to develop treatments that reduce cancer recurrence and mortality while having minimal detrimental effect on quality of life and comorbidity.

Adjuvant Therapy Background

The breast cancer mortality rate fell 24% between the years 1990 and 2000 for women aged 30 to 79 years.[4] This improvement in breast cancer mortality resulted from both early detection through screening and advancements in adjuvant treatment of early-stage disease. Depending on the model of risk reduction, adjuvant therapy has been estimated to be responsible for 35% to 72% of that reduction.[5] Adjuvant treatment of breast cancer is designed to treat micrometastatic disease or breast cancer cells that have escaped the breast and regional lymph nodes but have not yet established an identifiable metastasis. Treatment at this point is aimed at reducing the risk of future recurrence, thereby reducing breast cancer–related morbidity and mortality.

The time required for a micrometastasis to develop into clinically relevant metastatic disease is variable and relates to the growth rate and invasive characteristics of the primary tumor. For example, high-grade, estrogen receptor (ER)-negative, HER2-positive breast cancer is most likely to recur within the first 2 years following adjuvant therapy. Low-grade ER-positive breast cancers, on the other hand, are known to recur at a relatively constant rate for up to 25 years after primary therapy. Adjuvant treatment, then, is only effective if two conditions are met: (1) the patient's competing causes of mortality allow her to live long enough to see the reduction in recurrence, and (2) the treatment itself doesn't result in toxicities that are worse than the cancer recurrence it prevented. Therefore, it is paramount to factor in the treatment's potential to reduce risk against the patients' breast cancer–independent life expectancy and the potential toxicity of the therapy.

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