More on Breast Cancer in the Elderly
Abstract & Commentary
By William B. Ershler, MD, Editor, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC.
Synopsis: In a national survey conducted in Italy, data from 1085 women 65 years and older with newly diagnosed breast cancer was analyzed with regard to stage at presentation, histological features and treatments provided. By dividing the overall cohort into age subsets, the data indicate that those in the oldest group are more likely to present with larger tumors and also be treated in the adjuvant setting with endocrine manipulation alone. However, the oldest group were more likely to be hormone receptor positive. Other features of tumor aggressiveness, such as Ki67 and Her-2-neu expression were not significantly different across the various age subsets.
Source: Mustacchi G, et al. Ann Oncol. 2007;18:991-996.
Oncologists have become increasingly aware of geriatric issues relating to cancer management. These issues are particularly relevant to breast cancer because the majority of patients are over the age of 65 years and there are important and well recognized age-associated differences in tumor biology, screening and treatment. To achieve a better understanding of current attitudes and practices, the National Oncological Research Observatory on Adjuvant Therapy (NORA), operational throughout Italy, consecutively enrolled over 3500 breast cancer patients from 2000 through 2002, of which 1085 were 65 years or older. Of these, 40% were aged 65-69 years, 31% were 70-75 years and 29% were older than 75 years.
The analysis undertaken pertained to relevant clinical parameter and were described in the context of the three age subsets: 65-69, 70-75, and >75 years. A summary of their findings are as follows:
Diagnosis: Almost 50% of cases were diagnosed by self-exam and the percentage increased significantly by age group. Approximately 40% of those in the 65-69 year old group discovered their breast cancer by self exam compared to nearly 70% for those over 75 years. Conversely, routine periodic screening uncovered the breast cancer in 31% of those patients in the 65-69 year old group compared with only 11% in the over 75 year old group.
Comorbidities: Not surprisingly, the number of comorbidities increased with age. Significant comorbid disease was reported in 38% of those between 65-69 years compared with 70% for those over 75 years.
Tumor biology: Although histological type did not vary significantly among the three age subsets, tumor size was related to age. The number of T1 tumors decreased from 57.4% to 50.8% to 46.0% for the groups aged 65-69 years, 70-75 years, and >75 years respectively (c2 for trend = 12.430; P = 0.0004). Reciprocal increases in larger tumors were seen with each advancing age group.
In contrast, hormone receptor positivity increased with age. Overall, 85.5% had at least one positive receptor (estrogen or progesterone) and 67.9% were positive for both. Estrogen and Progesterone positivity was present in 63.6%, 68.6%, and 73.1% for groups aged 65-69 years, 70-75 years, and >75 years respectively (c2 for trend = 7.886; P = 0.005). Her-2-neu/c-erB2 status and proliferation index, evaluated by Ki67/MB1 staining, were not different in the age groups.
Axillary node dissections were performed in 95.5% of this group. Overall, 56.7% had negative nodes, 23.9% had one to three positive nodes, 12.3% had 4-10 positive nodes and 7.1% had >10 positive nodes, and there was no age-related difference. However, the median number of examined nodes declined with age of the patient (c2 for trend = 10.856; P = 0.001).
Treatment Decisions. Of the entire series, only 4.1% did not receive some form of systemic adjuvant treatment. Overall, 52.4% received endocrine therapy alone, 13% chemotherapy alone, and 30.4% both endocrine and chemotherapy. The use of endocrine therapy alone increased significantly with age (37.1% to 51.9% to 74.8% for groups aged 65-69 years, 70-75 years, and >75 years respectively and conversely, chemotherapy (alone or followed by endocrine treatment) decreased from 62.2% to 44.7% to 17.2% for groups aged 65-69 years, 70-75 years, and >75 years respectively (2 for heterogeneity = 146.51; P = 0.001).
This extensive survey performed throughout Italy was designed to be representative of the practice patterns as a whole, as great care was taken to include academic and community practices distributed throughout the country.1 This report includes data only for the over 65 year olds and demonstrates changes in stage at presentation, hormone receptor positivity, and treatment aggressiveness within the age group subsets. None of the findings will come as much of a surprise to practicing oncologists, although the data is a valuable addition to the literature, providing evidence for trends that we knew from experience to be likely. It was a little surprising to see the high number of axillary node dissections performed (95.5% of the entire group had pathological analysis of axillary nodes, albeit a slightly reduced number of nodes per patient was available for the oldest subset). Similarly impressive was the observation that only 4% of the group received no form of systemic adjuvant therapy. The detailed and careful NORA methodology1 make it unlikely that there was sample bias such that only the most robust of the elderly were included. This is somewhat in contrast to current perceptions regarding workup and treatment of breast cancer in the elderly, particularly those of very advanced age or with comorbidities.2-4
Measures of tumor aggressiveness, such as histological features, markers of proliferation or the over expression of Her-2-neu were not demonstrably different within the various subsets presented here. However, it will be of interest to see the entirety of the NORA data in this regard because differences between young and old might be much more apparent than when comparing old vs very old, as in the current report.
The NORA report is a welcome addition to the literature. There has been a substantial development of interest in geriatric oncology and this represents the largest observational series of elderly breast cancer patients. We look forward to ongoing analysis with regard to treatment success and overall survival in this well characterized cohort.
1. Cazzaniga ME, et al. Adjuvant systemic treatment of early breast cancer: the NORA study. Ann Oncol. 2006;17(9):1386-1392.
2. Bouchardy C, et al. Undertreatment strongly decreases prognosis of breast cancer in elderly women. J Clin Oncol. 2003;21(19):3580-3587.
3. Gennari R, et al. Breast carcinoma in elderly women: features of disease presentation, choice of local and systemic treatments compared with younger postmenopausal patients. Cancer. 2004;101(6):1302-1310.
4. Giordano SH, et al. Breast cancer treatment guidelines in older women. J Clin Oncol. 2005;23(4):7837-7891.