Node-Negative Breast Cancer in Very Young Women Requires Tailored Adjuvant Therapy
Node-Negative Breast Cancer in Very Young Women Requires Tailored Adjuvant Therapy
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: Breast cancer in women younger than age 35 is uncommon, but is known to be associated with more negative clinical outcomes. In the current analysis of prospective data gathered at the European Institute of oncology, very young patients (< 35 years of age) with locally resected, lymph-node-negative breast cancer were compared to similarly staged 'less young' patients (35-50 years of age). Tumors were found to have more aggressive features in the very young, and clinical outcomes were worse.
Source: Colleoni M, et al. Role of endocrine responsiveness and adjuvant therapy in very young women (below 35 years) with operable breast cancer and node negative disease. Ann Oncol. 2006;17:1497-1503.
Breast cancer occurring in very young women (eg, younger than 35 years) accounts for 2% of all cases and is considered a more aggressive disease than in older patients.1,2 Several factors might be responsible for this, but included might be the reluctance of very young patients to receive adjuvant hormonal therapy. The aim of this study from the European Institute of Oncology was to investigate the most recently available details of tumor biological characteristics and clinical outcomes in 'very young' (< 35 years of age) with node-negative breast cancer and compare these with 'less young' premenopausal patients (35-50 years of age).
Of the 4,231 patients with breast cancer operated at the European Institute of Oncology (EIO) between April 1997 and December 2001, there were 979 premenopausal patients with node-negative disease. Of these, 841 were evaluable under the current protocol. (Those who had received neoadjuvant therapy or who had a history of prior malignancy were excluded.) Of the 841 patients, 101 (12%) were 'very young' and 740 (88%) were 'less young'. 'Very young' patients were more likely to have tumors > 2 cm (35.6% vs 24.2%; P = 0.002), grade 3 (48.5% vs 31.9%; P = 0.009) and with elevated Ki-67 expression (62.4% vs 50.7%; P = 0.002). By multivariate analysis, a statistically significant difference in disease-free interval (DFS) (HR, 4.44; 95% confidence interval [CI], 2.53-7.78; P < 0.0001), risk of distant metastases (DDFS) (HR, 3.23; 95% CI, 1.32-7.94; P = 0.011) and overall survival (OS) (HR, 2.89; 95% CI, 1.06-7.87; P = 0.038) for the very young compared to the less young patients. For the subgroup with endocrine responsive tumors, the age differences were also apparent (DFS, HR, 5.17; 95% CI, 2.72-9.83; P ≤ 0.0001; DDFS, HR, 3.76; 95%CI, 1.33-10.6; P = 0.013; OS, HR, 4.71; 95% CI, 1.09-20.4; P = 0.039).
Thus, compared with older premenopausal, patients with node-negative breast cancer, those under the age of 35 years have a worse prognosis. This is particularly true for endocrine-responsive tumors.
Commentary
Premenopausal patients with node negative breast cancer, after adequate local treatment (breast conserving surgery or total mastectomy) plus axillary sentinel lymph node biopsy or complete axillary dissection, followed for some (particularly those who received breast conserving surgery) by post operative radiation are confronted with 'the next step.' For those who have endocrine unresponsive disease, systemic chemotherapy is typically prescribed. Chemotherapy is also recommended for those endocrine responsive disease who are at higher risk for recurrence (eg, occurrence of peritumoral vascular invasion, larger tumors, over expression of HER2/neu, increased proliferation markers). For the remainder of those with endocrine responsive disease, adjuvant endocrine therapy alone is most frequently recommended.3 In the current series, for the very young patients for whom hormonal therapy was not proposed, or for whom it was refused experienced four times the rate of relapse compared to the less young.
Thus, this report highlights two distinct features of breast cancer in young women. First, even for those who present with node negative disease, breast cancer appears more aggressive in the very young. In this series, the very young presented more frequently with poor prognostic features such as endocrine non-responsive disease, high grade and high proliferating fraction when compared to 'less young' premenopausal patients. Secondly, contributing to the difference in clinical outcomes, the data support the importance of hormonal therapy for those with estrogen responsive tumors. Whereas systemic chemotherapy might have ablative effect on ovarian function in older premenopausal patients, it is likely not to have the same effect in the very young. However, even for those ER+ very young patients who received tamoxifen plus ovarian function suppression, worse outcomes were observed when compared to similarly treated ER+ 'less young' patients. Accordingly, additional, more intensive hormonal therapies may be required to adequately suppress ovarian function in very young patients with ER+ breast cancer.
References
1. Walker RA, et al. Breast carcinomas occurring in young women (< 35 years) are different. Br J Cancer. 1996;74:1796-1800.
2. Albain KS, et al. Breast cancer outcome and predictors of outcome: are there age differentials? J Natl Cancer Inst Monogr. 1994;16:35-42.
3. Colleoni M, et al. Prediction of response to primary chemotherapy for operable breast cancer. Eur J Cancer. 1999;35:574-579
Breast cancer in women younger than age 35 is uncommon, but is known to be associated with more negative clinical outcomes.Subscribe Now for Access
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