Alternative Management Strategies for Local Disease

For most older women, treatments offered should be similar to those considered for younger women. However, alternative, less aggressive approaches to local therapy have been sought for older women, particularly for those in whom life expectancy is very limited or who are unable or unwilling to undergo standard therapy. Surgery or tamoxifen alone have been compared to each other and to combination therapy as the primary treatment for localized breast cancer in older women. Tamoxifen alone has been studied extensively as the initial treatment.

In general, tamoxifen instead of surgery for localized breast cancer results in an initial response rate up to 70%. The median time to response is approximately 3 months (range, 5-124 weeks), and responses can be durable in a large number of patients. Relapse rates with tamoxifen alone are high, however, and additional local therapy is necessary in more than 50% of patients.

In a recent series, Ciatto and colleagues reported on 120 women over age 69 treated initially with tamoxifen alone. After at least 6 months treatment, they report complete responses in 12 patients, partial response in 46 patients, and minor response or stable disease in 53 patients. Progressive disease was observed in 9 patients. Response duration was limited, and progression was observed increasingly over time. After 12 months, more than 50% of subjects were still showing response to treatment, which decreased to approximately 30% at 60 months follow-up. In a subset of 27 subjects, treatment response was strongly associated with tumor estrogen receptor content, progression being 100%, 43%, or 6% in subjects with 0%, 30% to 60%, or more than 60% immunostained cells, respectively.

When tamoxifen has been compared to surgery with or without tamoxifen, survival rates are not significantly different among patients who did not undergo surgery (ranging from 66% to 88% after 2 to 6 years for both groups). However, local recurrence rates are more common among patients treated with tamoxifen only, up to 56% in one series compared to 44% with surgery alone after 6 years follow-up. In the short term, tamoxifen appears to provide an acceptable alternative to surgical therapy in the older patient with early-stage hormone receptor-positive breast cancer. With longer follow-up, however, tamoxifen only delays surgical therapy for the majority. Primary management of early-stage disease with tamoxifen alone should probably be reserved for patients who have a very limited life expectancy or for patients who refuse surgical intervention. However, limited surgery without axillary dissection plus adjuvant tamoxifen may achieve a local regional control rate in older women comparable to that obtained with more aggressive strategies.

Alternative regimens of radiation therapy including weekly schedules have been considered for older patients who may be unable or unwilling to undergo daily radiation treatments or primary surgery. In two small retrospective analyses, weekly high dose per fraction breast irradiation was well tolerated in older women and resulted in encouraging local control rates. Treating 70 older women (median age, 81 years) with all stages of disease with daily tamoxifen and weekly radiation, Maher et al. reported an overall survival rate of 87%, disease-specific survival rate of 88%, and disease-free survival of 72% at a median follow-up of 36 months. The local control rate was 86% at 36 months. Based on such encouraging preliminary data, alternative radiation schedules should be explored further in clinical trials.