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SABCS 2011 Report – Age dependent variation in the management of breast cancer
by Dr Sunil Upadhyay – Age is the number one risk factor for the development of breast cancer. Not only the incidence but also the mortality from breast cancer increases with age. It is well known that in the western world the proportion of elderly to younger people is rising. In her presentation, Dr Arti Hurria from City of Hope, Duarte, California reminded the audience that in the year 1900 there were 3 million people over the age of 65, which increased by ten fold to 30 million by year 2000. It is estimated that there will be nearly 70 million Americans over the age of 65 by the year 2030. For oncologists this implies that there will be a continuous rise in the incidence of cancer in people over the age of 65. It is estimated that between 2010 and 2030, the incidence of cancer will increase by 11% in patients below the age of 65 but 67% in patients over the age of 65.1
It has also been observed that breast cancer outcomes have preferentially improved in women aged less than 75 years. The breast cancer age-specific mortality decline has been largest in the 29-40 age group (2.39%) but only 1.14% per year in women above the age of 75 years.2 Therefore, we need to pool our efforts to improve the mortality rate for breast cancer in the elderly population. We also need to understand why this is different. Could it be at least partly explained by differences in the pattern of care for the elderly population and younger adults? We do know that there are clear differences in the age-related use of mammography and older breast cancer survivors are less likely to get mammography, particularly beyond 75 years of age.3 Similarly, older patients with early stage breast cancer are less likely to undergo primary breast surgery and adjuvant radiotherapy.4 The same statistics hold true for adjuvant chemotherapy because older patients are less likely to get systemic cytotoxic therapy. There is evidence to show that only 10.9% of women over the age of 75 receive chemotherapy within 6 months of their diagnosis regardless of the stage of the disease at the time of initial diagnosis.5 The question is why are these patterns of care so different? It may be due to the fact that although screening mammography decreases breast cancer mortality, the data for women over 70 years of age is lacking. Similarly, although adjuvant chemotherapy is well proven to decrease breast cancer mortality, the majority of breast cancer trials of chemotherapy included too few women above the age of 70 for the data to be reliably informative as to whether it confers any net survival gain among this cohort.6,7 In other words, perhaps we need more reliable data from the older population to be able to offer them similar care with confidence.
The good news is that such evidence base is widening. Key studies are being conducted focusing on the treatment of the older population. Based on 7 randomised trials and an estimated 869 deaths in 1571 women, the results of a Cochrane review showed no benefit in respect to survival for either surgery or primary endocrine therapy in women above the age of 70 with operable breast cancer. However, women who had surgery were less likely to relapse than women on primary endocrine therapy (HR 0.55, p=0.0006). The authors concluded that surgery controls breast cancer better than tamoxifen alone in older women but does not extend survival. Both interventions were associated with adverse events.8 Therefore, similar to the younger age group, patients suitable for surgery must be offered it. The type and extent of surgery has to be decided on an individual basis. The international breast cancer study group trial did not show any difference in the QoL, axillary recurrence, DFS and OS outcome between axillary surgery (n=234) vs no axillary surgery (n=239) in patients who were over the age of 60 with clinically negative axilla.9 Similarly another randomised trial in patients over the age of 70 with clinical stage I, ER positive tumours treated with post lumpectomy radiotherapy + tamoxifen compared with tamoxifen alone at a median follow-up of 12 years was reported to show modest increased risk of local recurrence (9 vs 2%) without radiotherapy but no impact on survival.10
The rationale for adjuvant systemic therapies like endocrine therapy, chemotherapy and trastuzumab is to decrease the risk of relapse and breast cancer related mortality; although many might be already cured without adjuvant systemic therapy. As far as the older age group is concerned, because of limited toxicity, endocrine therapy is frequently prescribed and the benefit from endocrine therapy is maintained with age. Prophylactic use of bisphosphonates, calcium and vitamin D supplements with close monitoring of bone mineral density can well maintain the bone health in these individuals. However, the use of chemotherapy remains one of the most challenging decisions and one has to balance between risk and benefits. Moreover, adjuvant chemotherapy shows decreasing benefit over the age of 60, particularly in oestrogen receptor positive tumours. Average life expectancy remains one of the hotly debated criteria along with co-morbidities and performance status. One can be looking at a healthy or not so healthy person with variable performance status and life expectancy, which needs to be utilised in the decision-making. The numbers of elderly patients in the published randomised trials were small hence it is hard to make a reliable estimate. However, there is emerging data to indicate the benefits of standard adjuvant chemotherapy in the elderly population.11 Careful selection of patients should minimise the treatment related early and late side effects with optimum benefit. Use of reliable geriatric assessment tools to define good and poor health need to be implemented. Factors other than chronological age that predicts the morbidity and mortality in older patients like functional status, co-morbidities, nutritional status, social activity and support, vital organ function and poly-pharmacy should predict the chemotherapy tolerance and outcome. Performance status is not the most sensitive tool to predict tolerance. The ongoing trials on the use of adjuvant chemotherapy in the elderly should provide further evidence soon. A geriatric assessment needs to be routinely incorporated in to the prospective studies. Abstract ES6-3. SABCS 2011
References:
1. Smith B, Smith G, Hurria A, Hortobagyi G, Buchholz T. JCO 2009; 27: 2758-2765. doi: 10.1200/JCO.2008.20.8983
2. Smith B, Jing J, Mclaughlin S, Hurria A, Smith G et al. JCO 2011; 29: 4647-4653. doi: 10.1200/JCO.2011.35.8408
3. Keating N, Landrum M-B, Guadagnoli E, Winer E, Ayanian J. JCO 2006; 24(1): 85-94. doi 10.1200/JCO.2005.02.4174
4. Schonberg M, Marcantonio E, Li D, Silliman R, Long E, McCarthy E. JCO 2010; 28(12): 2038-2045. doi: 10.1200/JCO.2009.24.6314
5. Du X, Goodwin J. JCO 2001; 19(5): 1455-1461
6. Nelson H, Tyne K, Naik A, Bougatsos C, Chan B, Humphrey L. Ann Intern Med 2009; 151: 727-737
7. Early Breast Cancer Trialists Collaborative Group (EBCTCG). Lancet 2005; 365(9472): 1687-1717. doi:10.1016/S0140-6736(05)66544-0
8. Hind D, Wyld L, Beverley C, Reed MW. Cochrane Review, published online July 16, 2008
9. International Breast Cancer Study Group. Trial 10-93, JCO Jan 20, 2006; 24: 337-344
10. Hughes K, Schnaper L, Berry D, Cirrincione C et al. New Eng J Med 2004; 351: 971-977
11. Muss H, Berry D, Cirrincione C, Theodoulou M et al. New Eng J Med 2010; 360: 2055-2065
