Factors That Predict Relapse after Neoadjuvant Chemotherapy for Breast Cancer
By William B. Ershler, MD, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC and is Editor of Clinical Oncology Alert. Dr. Ershler is on the speaker’s bureau for Amgen and does research for Ortho Biotech.
Abstract & Commentary
Synopsis: Breast cancer patients who receive neoadjuvant chemotherapy and achieve pathologic complete remission have a favorable outlook. However, some go on to develop recurrent disease. In this report, the experience at a single institution indicates that premenopausal patients with more advanced primary lesions and fewer axillary nodes resected are more likely to develop distant metastases.
Source: Gonzalez-Angulo AM, et al. Factors predictive of distant metastases in patients with breast cancer who have a pathologic complete response after neoadjuvant chemotherapy. J Clin Oncol. 2005;23:7098-7104.
Neoadjuvant chemotherapy has become standard practice for locally advanced or inflammatory breast carcinoma and is an increasingly popular treatment strategy for large operable breast cancer. This approach has been shown to facilitate breast conservation and can produce disease-free survival (DFS) and overall survival (OS) equivalent to standard adjuvant chemotherapy.1,2 One distinct and useful aspect of the neoadjuvant approach is that important information is gained in assessing the response to therapy. For example, prospective trials have demonstrated that patients who have a pathologic complete remission (pCR) of the primary tumor have significantly improved DFS and OS when compared to those who do not have pCR.1-3 Nonetheless, some patients (13-25%) who achieve pCR will later develop recurrence.1,3,4
The purpose of the current analysis was to identify what clinical or pathologic features of patients who achieve pCR after neoadjuvant breast cancer chemotherapy predict disease recurrence. For this, Gonzalez-Angulo and colleagues from the M.D. Anderson Cancer Center performed a retrospective review of 226 patients at that institution who were shown to have a pCR after neoadjuvant therapy. Of these, 11% were known to have inflammatory breast cancer (IBC) at the time of diagnosis. Of the remainder, 2% were clinical stage (CS) I, 36% CS II, 27% CS IIIA, 23% CS IIIB, and 12% CS IIIC. Although not all patients were treated identically, 95% had received anthracycline-based regimens and 42% also received taxane.
After a mean follow-up of 63 months, there were 31 patients with recurrent disease (distant metastases). By multivariate Cox regression analysis, advanced pretreatment clinical stage (CS IIIB, IIIC, or IBC), identification of < 10 lymph nodes and premenopausal status predicted recurrence. Freedom from distant metastases at 10 years was 97% for no factors, 88% for 1 factor, 77% for 2 factors and 31% for 3 of these factors present at diagnosis.
Commentary
Thus, although only a relatively small percentage of breast cancer patients who achieve a pCR have systemic recurrence, 3 factors were identified which independently predict for the development of distant metastases. Premenopausal patients with stage IIIB or greater and less than 10 axillary nodes resected were more likely to have a poor outcome, despite achieving pCR. In the traditional adjuvant setting, nodal involvement, tumor size, nuclear grade, and hormone receptor status have been described as determinants of recurrence risk.5 New methods are currently under exploration to further define recurrence likelihood. For example, gene expression profiles from biopsy-obtained (pre-treatment) breast cancer tissue was used to predict response to neoadjuvant therapy by Chang and colleagues.6 By examining the expression of 92 selected genes, response to taxane-based therapy had a 92% positive and 83% negative predictive value.
Yet, in the community, clinical features remain the most useful determinants of prognosis. In this regard, achieving pCR is certainly the most important predictor of favorable outcome for those receiving neoadjuvant chemotherapy. For those individuals, the greatest chance of relapse appears to be in premenopausal patients with locally advanced or inflammatory presentations and less than 10 axillary nodes at the time of surgery.
References
1. Fisher B, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998;16:2672-2685.
2. van der Hage JA, et al. Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol. 2001;19:4224-4237.
3. Chollet P, et al. Prognostic significance of a complete pathological response after induction chemotherapy in operable breast cancer. Br J Cancer. 2002;86:1041-1046.
4. Kuerer HM, et al. Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol. 1999;17:460-469.
5. Abrams JS. Adjuvant therapy for breast cancer—results from the USA consensus conference. Breast Cancer. 2001;8:298-304.
6. Chang JC, et al. Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer. Lancet. 2003;362:362-369.
Breast cancer patients who receive neoadjuvant chemotherapy and achieve pathologic complete remission have a favorable outlook. However, some go on to develop recurrent disease. In this report, the experience at a single institution indicates that premenopausal patients with more advanced primary lesions and fewer axillary nodes resected are more likely to develop distant metastases.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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