Defining Minimal Therapy for Localized Breast Cancer in Older Women
Abstract & Commentary
By William B. Ershler, MD, Editor
Synopsis: In a series of 354 elderly breast cancer patients treated with conservative surgery and tamoxifen but without axillary dissection or radiotherapy followed for 15 years, the cumulative incidence of developing axillary disease was 4.2%, and of developing local recurrence was 8.3%. Of the 354 subjects, 268 had died over the 15-year period, 17% of breast cancer and (83%) from causes other than breast cancer.
Source: Martelli G, et al. Elderly breast cancer patients treated by conservative surgery alone plus adjuvant tamoxifen. Fifteen-year results of a prospective study. Cancer. 2008;112:481-488.
In elderly patients with early breast cancer and without palpable axillary lymphadenopathy, axillary surgery, sentinel lymph node biopsy, and postoperative radiotherapy to the residual breast may not be necessary because of reduced life expectancy, effectiveness of hormone therapy in achieving long-term disease control, and generally favorable biologic behavior of breast cancer in elderly patients.
The current report is an update of a cohort of elderly breast cancer patients who were treated with local resection and tamoxifen, but without axillary node dissection, radiation or chemotherapy.1 This cohort now includes 354 women aged 70 years who had primary, operable breast cancer and no palpable axillary lymph nodes. Women who had resection margins in tumor tissue were excluded. Endpoints were cumulative incidence of axillary disease, cumulative incidence of ipsilateral breast tumor recurrence (IBTR), and breast cancer mortality.
After a median follow-up of 15 years, a total of 31 patients had developed ipsilateral breast tumor recurrence (IBTR) at a median of 3 years after surgery (range, 4 months to 16 years). The cumulative incidence of IBTR was 8.3% (7.3% in pT1 tumors). Patients with local recurrence were treated by conservative surgery. Of these 31 patients, 5 went on to develop systemic metastases and died of this condition and 14 others died of conditions other than breast cancer. Over the 15 year follow-up, only 16 patients developed ipsilateral axillary disease as their first event, at a median of 3 years (range 10 months to 15 years) after surgery (crude cumulative incidence for axillary recurrence was 4.2%). Axillary disease was treated by delayed dissection in 5 patients, radiotherapy in 9 patients, and second-line hormone treatment in 2 patients. Nine of the 16 patients developed distant metastases and died from this condition. Thirty-one patients developed distant metastases as their first event and all received second-line hormone treatment. All but one of these patients died from this condition. Thus, of the 268 patients who died during follow-up, 46 (17%) died of causes directly related to their breast cancer whereas 222 patients (83%) died from causes unrelated to breast cancer.
Commentary
The findings of this study are important. For older women with resectable breast cancer and without palpable axillary nodes, the paradigm of axillary node dissection followed by radiotherapy and then hormonal therapy may be more than is needed. In fact, in this cohort of 354 women over the age of 70 years treated with resection and tamoxifen and followed for a median of 15 years, the risk of tumor recurrence or breast cancer related death was small. The great majority (83%) of the 262 women who died during this 15 year follow-up, did so of causes unrelated to breast cancer. This is consistent with other reports in which comorbidities in elderly breast cancer patients prove often to be of greater importance than the breast malignancy.2
Two major considerations are at play here. First is the issue of competing causes for mortality and the importance of comorbidities at the time of diagnosis of breast cancer. Secondly, the natural history of breast cancer in the elderly is likely different. Breast tumors arising in this age group are more likely to be ER/PR positive and are demonstrably less likely to harbor markers of aggressive disease (ie, lower rates of tumor cell proliferation, a lower expression of the human epidermal growth factor receptor 2 (HER2), a higher frequency of diploidy, and a lower frequency of p53 accumulation).3-5 Thus, the low rate of recurrence, particularly in the ipsilateral axilla (having not had axillary dissection) or locally (having not had radiation) may reflect a combination of the efficacy of tamoxifen to control hormone receptor positive tumors as well as the more indolent nature of the tumor itself.
Thus, these findings will probably not surprise the practicing oncologist, although the very low cumulative risk of ipsilateral breast tumor recurrence was striking in these patients who received no adjuvant radiation therapy. However, others have reported similar observations. For example, Veronesi and colleagues found that 4 years after partial mastectomy, and in the absence of post-operative irradiation, the local recurrence rate of breast cancer was 18% in women younger than 55 years and 3% in those older than 55.6 And, although it is difficult in a non-randomized or controlled trial to make firm conclusions, the findings are consistent with those from the National Surgical Adjuvant Breast and Bowel Project(NSABP)-04 trial that demonstrated after 20 years, overall survival and distant relapse-free survival in breast cancer patients following radical mastectomy were equivalent to those who underwent surgery without axillary dissection.7
Thus, elderly patients with early breast cancer and no clinically-evident axillary adenopathy may be safely treated by conservative surgery and hormonal therapy but without axillary dissection or postoperative radiotherapy, provided that surgical margins are in tumor-free tissue. Sentinel lymph node biopsy is also unnecessary because of the low cumulative incidence of axillary disease, and axillary surgery can be reserved for the small proportion of patients who later develop overt axillary disease. Certainly, this approach should reduce surgical complications and morbidity associated with axillary dissection as well as the logistical difficulties associated with radiotherapy. However, clinicians should be aware that the current series included carefully selected patients who had resectable primaries (margins free) and no evidence for axillary adenopathy. For those with more advanced disease at presentation, the current data would not apply and the higher risks of local or axillary recurrence must be weighed against those of axillary dissection and local irradiation on a case by case basis, keeping in mind the importance of existing comorbidities.
References
1. Martelli G, et al. British J Can. 1995;72(5):1251-1255.
2. Yancik R, et al. Effect of age and comorbidity in postmenopausal breast cancer patients aged 55 years and older. JAMA. 2001;285(7):885-892.
3. Daidone MG, et al. Primary breast cancer in elderly women: biological profile and relation with clinical outcome. Crit Rev Oncol Hematol. 2003;45(3):313-325.
4. Diab SG, et al. Tumor characteristics and clinical outcome of elderly women with breast cancer. Journal of the National Cancer Institute 2000;92(7):550-6.
5. Pierga JY, et al. Breast. (Edinburgh, Scotland) 2004;13(5):369-375.
6. Veronesi U, et al. Ann Oncol. 2001;12(7):997-1003.
7. Fisher B, et al. N Eng J Med. 2002;347(16):1233-1241.
In a series of 354 elderly breast cancer patients treated with conservative surgery and tamoxifen but without axillary dissection or radiotherapy followed for 15 years, the cumulative incidence of developing axillary disease was 4.2%, and of developing local recurrence was 8.3%. Of the 354 subjects, 268 had died over the 15-year period, 17% of breast cancer and (83%) from causes other than breast cancer.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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