Pathologic Predictors of Tumor Response to Preoperative Chemotherapy in Locally Advanced Breast Carcinoma

Abstract

Tumor response to preoperative chemotherapy varies from complete to partial to none. To evaluate pathologic predictors of tumor response to preoperative chemotherapy, we reviewed 287 cases of locally advanced breast carcinoma treated with chemotherapy prior to definitive surgery. The patients ranged in age from 18 to 79 years (mean, 48 years). There were 77 (26.8%) patients with stage I 1 disease, 194 (67.6%) with stage 111 disease, and 16 (5.6%) with stage IV disease. Following the initial diagnosis of invasive carcinoma (by fine-needle aspirate or cutting needle biopsy), the patients received three to four cycles of both doxorubicin-based and cyclophosphamide-based regimens followed by mastectomy or lumpectomy with axillary dissection. The pathologic parameters that were evaluated included stage, clinical tumor size, and tumor nuclear grade (NG). The latter was performed on fine-needle aspirates using Black's nuclear grading system wherein NG I was considered well differentiated; NG2, moderately differentiated; and NG3, poorly differentiated. Based Dr. Abu-Farsakh is now an attending pathologist at The University of Jordan, Amman, Jordan 0 1995 Blilckwell Science Inc , 1075-122X/95/$10.50/0 rlv B r m t lournal, Volume I, Number I, 1997 96-101on pathologic examination of the resected specimens, tumor responses were categorized into complete response, partial response, no response, or progressive disease. The overall response rate was 71% (12% complete and 59% partial responses). In univariate analyses, tumor size and nuclear grade were significantly related to pathologic tumor response to chemotherapy (p = 0.04 and p = 0.0003, respectively), while disease stage was not (p = 0.1 7). In multivariate analyses, size remained significant even when NG was present in the equation (p = 0.01 3). Similarly, when size was included. NG remained significant (p = 0.002). NG3 tumors showed better response than NG2 or NG1 tumors did. While 19.3% of NG3 tumors showed complete response, none of the NG 1 tumors completely responded to chemotherapy. Initial tumor size was inversely proportional to degree of tumor response. Our findings indicate that tumor clinical size and nuclear grade are important independent predictors of response to preoperative chemotherapy and that poorly differentiated tumors and small tumors showed the most response.nduction chemotherapy (also known as neoadjuvant

Residual Cancer Burden in Locally Advanced Breast Cancer: A Superior Tool

“…Other prognostic markers that may have different implications in labc include tumour nuclear grade, with poorly differentiated tumours being more likely than well differentiated tumours to respond to neoadjuvant chemotherapy 9,17. Also, increased expression of the human nuclear protein Ki-67, which is associated with cell proliferation and is used in routine pathology as a “proliferation marker” to measure the growth fraction of cells in human tumours, has been correlated with a better response to chemotherapy 18,19.…”

“…Therefore, additional surrogate endpoints for outcome and survival are needed. Also, many of the classic biologic predictive and prognostic factors such as hormone receptors and tumour grade may have implications that are different in labc than in earlier stages of the disease 5–9. To advance our understanding of this disease, identification of reliable markers that would lead to better disease classification and improved treatment outcomes is desirable.…”

Update on Locally Advanced Breast Cancer

“…Since response to chemotherapy is an important predictor of survival, many investigators have studied markers that may predict response to chemotherapy. For patients treated with anthracycline-based induction chemotherapy, small tumor size, high nuclear grade, high proliferation index (Ki67), and coexpression of HER-2/neu and topoisomerase II have been associated with greater response rates [53][54][55][56][57][58]. Conversely, mutation of the p53 gene is associated with a lower response rate to chemotherapy [59,60].…”

Is Axillary Lymph Node Dissection Necessary in Routine Management of Breast Cancer? No.

“…They should promptly have a mastectomy and complete axillary node dissection to attempt regional disease control, if they are clinically operable. If patients demonstrate a complete or substantial partial response with neoadjuvant chemotherapy, which is reported to occur in 70-80% (4), the prognosis is far better, and long-term, disease-free survival is possible (44,(77)(78)(79)(80). Thus, the treatment of advanced primary breast cancer should begin with neoadjuvant chemotherapy, to observe the response of the undissected axilla and the biopsied but unremoved primary breast cancer.…”