HER-2 Neu Overexpression in Older Women with Breast Cancer
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 retrospective review of data from 153 breast cancer patients 70 years and older who were treated with wide local excision and irradiation for early stage breast cancer, Her-2 neu overexpression was shown to predict axillary nodal involvement and be associated with nodal and distant failure and reduced cause-specific survival. Her-2 neu may prove a useful biomarker for decisions regarding which elderly patients will benefit from more aggressive management.
Source: Poltinnikov IM, et al. Impact of Her-2 neu overexpression on outcome of elderly women treated with wide local excision and breast irradiation for early stage breast cancer: An exploratory analysis. Am J Clin Oncol. 2006;29:71-79.
Optimal treatment for older patients with breast cancer remains controversial and investigation in this regard is imperative as we acknowledge the median age for breast cancer is approximately 70 years and consider the population demography which indicates a shift towards older age. Without sufficient data to direct otherwise, breast cancer management in the elderly typically remains less aggressive. For example, surgical evaluation of the axilla is more often omitted and chemotherapy is less frequently prescribed, particularly in the adjuvant setting. It would be inappropriate to criticize the practicing oncologist for this because most are aware that elderly patients are less frequently included in clinical trials, and those who are included may not be representative of the typical breast cancer patient in their age group. Thus, there is yet to be established guidelines for the treatment of 'typical' older breast cancer patients, particularly those with existing comorbidities and/or functional impairments.
Poltinnikov and colleagues at the Kimmel Cancer Center of Jefferson Medical College (Philadelphia) have performed a retrospective analysis of elderly (> 70 years) women with stage I-II breast cancer who were managed with wide local excision and breast irradiation. The purpose of their retrospective review was to determine the clinical importance of overexpression of Her-2 neu with regard to disease recurrence and overall survival in this population. Of the 153 patients who met age and stage criteria, Her-2 neu data was available for 106; 22% of whom were Her-2 neu positive and 78% negative. Her-2 neu positivity was significantly associated with high histological grade (P = 0.008), T2 stage (P = 0.001) and positive axillary lymph nodes (P = 0.02) among 73 patients who had surgical assessment of axilla. Overall, only 15 patients (14%) received chemotherapy. There were no recurrences in the breast. Her-2 positivity predicted for nodal and distant failure (NDF) and cause-specific survival (CSS). Projected 5-year freedom from NDF was 70% for Her-2 neu positive and 97% for Her-2 neu negative patients. CSS was 86% for Her-2 neu positive and 98% for Her-2 negative patients (P < 0.01). Overall survival was no different between Her-2 neu positive and Her-2 negative patients (80% vs 85%). Thus, similar to the trend in younger patients, Her-2 neu positivity confers clinically more aggressive disease.
There is a commonly held notion that breast cancer in older women is less aggressive, and this may enter the practicing oncologist's mind when developing treatment strategies, particularly for those older women who present with early stage disease. Yet, an emerging literature, primarily retrospective analyses, demonstrates that under-treatment, such as omission of surgical evaluation of the axilla and elimination of adjuvant radiation and chemotherapy, strongly decreases prognosis of elderly breast cancer patients.1-3 However, for the practitioner confronted with an older patient, other factors must also be considered, including comorbidities and functional impairments which are both more frequent with advancing age.4 As we gather data on older patients with breast cancer it is important to note similarities and differences with regard to tumor biology and predicted clinical course as they occur in younger patients.
The current retrospective analysis is illustrative. In their series of elderly women who had breast conserving primary management, most patients (69%) had surgical evaluation of the axilla as well and 23% (17/73) were found to have evidence of carcinoma in the axillary nodes. For those whose primary tumor was Her-2 neu positive, there was a significant increased risk of axillary node positivity. Furthermore, Her-2 neu positivity conferred a higher rate of nodal and distant failure and a worse cause-specific failure.
Oncologists faced with a decision whether or not to treat older women with breast cancer after excision and axillary node dissection may refer to data from prospective trials (most of which included a non-representative sample of older patients), for which computer models are now available (eg, www.adjuvantonline.com) that predict risk of relapse and death from breast cancer based upon patient's age, primary tumor size, histological grade and ER status. To the extent that this data is derived from those older patients who are otherwise 'fit' enough to meet trial entry criteria, there should be caution regarding extrapolation to the typical elderly patient. In this regard, biological markers of disease aggressiveness, such as the over expression of Her-2 neu (not yet included in available computer models) should be taken into consideration.
As with just about every clinical paradigm in medical oncology, the field awaits prospective trials to guide decision making with regard to typical geriatric cancer patients, including those with comorbidities and functional impairments. In the meantime, this report would indicate that those older women with primary tumors that overexpress Her-2 neu should not be considered to have indolent disease, and these individuals are among those that will more likely benefit from more aggressive management.
1. Bouchardy C, et al. Undertreatment strongly decreases prognosis of breast cancer in elderly women. J Clin Oncol. 2003;21:3580-3587.
2. Truong PT, et al. Age-related variations in the use of axillary dissection: a survival analysis of 8038 women with T1-ST2 breast cancer. Int J Radiat Oncol Biol Phys. 2002;54:794-803.
3. Joslyn SA. Radiation therapy and patient age in the survival from early-stage breast cancer. Int J Radiat Oncol Biol Phys. 1999;44:821-826.
4. Yancik R, et al. Effect of age and comorbidity in postmenopausal breast cancer patients aged 55 years and older. JAMA. 2001;285:885-892.