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Treating Advanced Breast Cancer in the Older Woman

Treating Advanced Breast Cancer in the Older Woman

ABSTRACT: ABSTRACT: As half of all breast cancers occur in patients beyond the age of 65 and a quarter beyond the age of 75, a significant number of patients with metastatic breast cancer are elderly. New hormonal therapies, such as aromatase inhibitors, appear to have favorably improved the survival of these patients. Side effects such as osteoporosis or cognitive issues appear manageable. Information specific to elderly patients has recently emerged in the field of chemotherapy for metastatic breast cancer. This article reviews data on anthracyclines, taxanes, capecitabine (Xeloda), gemcitabine (Gemzar), trastuzumab (Herceptin), and bevacizumab (Avastin). For most patients in this setting, sequential single-agent chemotherapy appears at this time to be the preferred course of treatment.

There is good news for metastatic breast cancer patients: Their survival is increasing—from 27% at 3 years in the early 1990s to 44% in the late 1990s, if they are metastatic at presentation (Figure 1).[1] Although these retrospective data do not allow a clear assessment of causality, it is a reasonable hypothesis that the answer lies in the dramatic increase of treatment options available for this disease and their more widespread application. This article will review to what extent this is also true for the elderly, and how well these drugs are suited to this population.

As age advances, the proportion of aggressive breast cancers with either high-grade, estrogen-receptor (ER)/progesterone-receptor (PR) negativity, or HER2 overexpression decreases. However, such tumors can still develop even in women who are in their 90s. Although these types of tumors pose a higher risk of relapse, even ER/PR-positive, HER2-negative, and lower-grade tumors can reoccur. In such cases, hormonal therapy should be considered.

Hormonal Therapy

The improvement in survival during the 1990s pertains mostly to hormone receptor-positive patients, which is good news for older patients and is likely due in large part to the arrival of the aromatase inhibitors in the armentarium. Antiestrogen therapy has few side effects, but two of them are somewhat more relevant to the elderly than to the young.

One issue is the risk of osteoporosis with aromatase inhibitors, an issue that was primarily raised in the adjuvant setting.[2] However, since certain women with good-prognosis metastatic cancer may undergo years of treatment, the issue should be kept in mind. A pair of large studies Z-FAST and ZO-FAST (Zometa/-Femara Adjuvant Synergy Trials)—are under way to assess whether zoledronic acid (Zometa) can prevent this bone loss. If the results are positive, it will be reassuring news for women with metastatic breast cancer, since the oncologic treatment itself often includes bisphosphonates.

The other potential problem is the cognitive impact of hormonal therapy. Much has been published about this issue, with often inconclusive results. A recent British study comparing patients enrolled in the ATAC trial (Arimidex, Tamoxifen, Alone or in Combination) to untreated controls with a neuropsychological battery found a similar negative impact on cognitive function for anastrozole (Arimidex), tamoxifen, or both agents combined.[3] The effect consisted mainly of a mild decrease in processing speed and verbal memory. The history of the cognitive impact of hormonal therapy, from estrogen replacement to antiestrogens, is a long and confused one. If there is any impact, it appears to be minor and should not preclude treatment.

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