Chemotherapy

The role of adjuvant chemotherapy in older women is controversial. Although earlier trials showed minimal benefit in older women, recent larger trials and the Oxford overview analyses have revealed that adjuvant chemotherapy results in modest benefits in postmenopausal women (Table 33.9). In the most recently published overview analysis, there were too few women in the 70 and older age group to draw conclusions about chemotherapy in this population, and few randomized trials have included many women over 70 years of age. Among women aged 50 to 69 years, chemotherapy for women with estrogen receptor-negative tumors resulted in a reduction in the risk of recurrence of 30% (±5%) compared to a reduction of 40% (±7%) in women less than 50 years of age. For women with estrogen receptor-positive tumors who will also benefit from tamoxifen, chemotherapy resulted in a decrease in the risk of recurrence of 18% (±4%) among women aged 50 to 69 years compared to 33% (±8%) proportional risk reduction in women less than 50 years of age.

An important question for older women with ER- positive tumors is whether adjuvant chemotherapy adds anything to the benefits of tamoxifen. The overview analysis, as well as individual studies, have demonstrated that combination therapy with tamoxifen and chemotherapy is better than the use of either treatment alone in women with estrogen receptor-positive tumors.

In the overview, combination therapy resulted in an overall reduction in the risk of both recurrence and death of 19% (±3%) and 11% (±4%), respectively, among women aged 50 to 69 compared to tamoxifen alone. Because the benefits of chemotherapy appear to decrease with age, however, the absolute incremental benefit of chemotherapy added to tamoxifen in older women with hormone receptor-positive tumors may be relatively small. In women with ER-positive disease of all ages, combination chemotherapy and tamoxifen resulted in a reduction in risk of recurrence and death of 52% (±8%) and 47% (±9%) respectively, compared to chemotherapy alone. The overview analysis also suggested that anthracycline-containing chemotherapy regimens are superior to non-anthracycline-containing regimens. However, concern about the inherent risk of cardiotoxicity with anthracycline-based chemotherapy mandates careful consideration of its use in older women in the adjuvant setting. Table 33.10 lists the standard adjuvant chemotherapy regimens for breast cancer.

The benefits of chemotherapy must also be weighed against the risks. The acute toxicities of standard chemotherapy regimens have been well studied, although largely in younger patient populations. These toxicities are generally short term in nature. Some degree of nausea with or without vomiting is common but usually controllable with modern antiemetics. Mild mucositis is occasionally seen, although it is almost never severe. Myelosuppression is nearly universal; however, a systemic infection occurs in less than 5% of patients. Total alopecia will occur in almost all patients who receive an anthracycline-based regimen (including doxorubicin or epirubicin), compared to approximately 50% of patients who receive CMF (cyclophosphamide, methotrexate, and 5-fluorouracil). Weight gain is also not uncommon among women who receive adjuvant chemotherapy. Addition of paclitaxel to adjuvant chemotherapy results in an incidence of severe neuropathy of less than 5%. An increased risk of thromboembolic disease has been observed in patients receiving chemotherapy, particularly when it is given concurrently with tamoxifen. Long-term risks include a risk of less than 1% of cardiotoxicity resulting in congestive heart failure with anthracycline-based therapy, as well as a very small risk of treatment-related leukemia. It is unclear whether these risks are increased further among older women, although the risk of cardiotoxicity is increased in patients with cardiac disease, which is more common in older women.