Notes: Abstract: Black women with breast cancer have significantly poorer survival rates, a more advanced stage distribution, and are diagnosed at younger ages compared to white patients in the United States. We evaluated tumor response and survival with respect to race and age after induction chemotherapy. The study population consisted of 303 patients (229 white, 74 black) registered in two prospective trials of induction chemotherapy for locally advanced breast cancer [stage II (T 〈inlineGraphic alt="geqslant R: gt-or-equal, slanted" extraInfo="nonStandardEntity" href="urn:x-wiley:1075122X:TBJ99071:ges" location="ges.gif"/〉 4 cm), stage III (noninflammatory), and stage IV (supraclavicular lymph node involvement only)] between 1989 and 1996. Chemotherapy regimens utilized 5-fluorouracil, cyclophosphamide, and doxorubicin (FAC). Response was defined as complete (CR, no clinical/radiographic detectable disease), partial (PR, 〈inlineGraphic alt="geqslant R: gt-or-equal, slanted" extraInfo="nonStandardEntity" href="urn:x-wiley:1075122X:TBJ99071:ges" location="ges.gif"/〉50% reduction in disease), minor (MR, 〈50% reduction), no change (NC), or progressive disease (PD). Median follow-up was 58 months; survival was calculated using the Kaplan–Meier method. There was no significant difference in age at presentation (54% of black patients compared to 58% of white patients 〈50 years of age). The black patients had significantly more advanced stages of disease at diagnosis (50% of black patients compared to 30% of white patients with stage IIIB disease; p = 0.03). For both age groups together, tumor response, 5-year overall survival (OS), and 5-year disease-free survival (DFS) rates were similar between the black and white patients. A trend was noted that the younger black patients were more likely to have a clinical CR or PR; this did not translate into a survival advantage. Despite the more advanced stage distribution for black women with breast cancer, induction chemotherapy yields high response rates (especially for younger black patients) and survival rates equivalent to white patients.

Notes: Abstract: Recent discussions have questioned the need or benefit of radical axillary lymphadenectomy for some patients as part of treatment for breast carcinoma. An evaluation of the need for discontinuous lymphadenectomy is presented with proposal to eliminate lymphadenectomy in the breast-conserving therapy of some patients.From 1977 through 1993, 101 breasts in 95 patients with breast carcinoma were treated by breast conservation without radical axillary lymphadenectomy.At median follow-up of 76 months, only four patients (4.0% of cancers) had occurrence of axillary disease requiring invasive evaluation of delayed clinically positive axillae. One of the four patients had negative nodes. Two patients had positive lymph nodes without recurrent disease in the ipsilateral breast or distant metastasis. The fourth patient had distant metastasis, and a positive fine-needle aspiration biopsy of an axillary lymph node was sufficient for diagnosis. Discontinuous radical axillary lymphadenectomy was neither technically different nor more difficult that primary lymphadenectomy.Some breast cancer patients may forego surgical evaluation of the axilla as part of their breast conservation therapy without compromise in adjuvant therapy decisions or detriment in outcome. The authors strongly recommend large prospective, clinical studies be performed in the near future.

Notes: Abstract: We performed a retrospective analysis of clinical course of 91 patients who developed both breast cancer and a chronic lymphoproliferative neoplasm and were seen at the M. D. Anderson Cancer Center between January 1, 1970 and December 30, 1991. The sample included 24 individuals who developed lymphoproliferative neoplasm first (Group A), 22 individuals with concurrent diagnosis of both malignancies (Group B), and 45 individuals who developed breast cancer first (Group C). The median time to diagnosis of secondary breast cancer and lymphoproliferative neoplasm was 66 months (range, 7–459) and 65 months (range, 0–334), respectively. A higher proportion of Group B lymphomas were low-grade (77% vs. 47% [Group A] vs. 37% [Group C] p = 0.009). Prior occurrence of either one of these malignancies did not affect the disease-specific survival from the second malignancy. However, continuing mortality from the first malignancy appeared to contribute to a poor overall survival following second malignancy. Group A included 8 patients who developed breast cancer following radiation therapy for Hodgkin's disease after a mean interval of 18 (± 4.3) years. Three of these individuals had coexisting ductal and lobular histology (vs. none of the individuals in Groups B and C, p = 0.02). Another interesting finding was the high incidence of multiple additional malignancies in this patient population. A total of 29 additional neoplasms occurred in 21 (23%) of the 91 study subjects. These malignancies involved a wide variety of organ sites and could not be attributed to the therapy for either the breast cancer or the lymphoma in most cases. The data suggest that individuals who develop both breast cancer and a lymphoproliferative neoplasm are at a high risk for multiple malignancies. Close surveillance of such individuals for additional malignancies and further studies to understand the molecular basis of this predisposition are warranted.?

Notes: 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 II disease, 194 (67.6%) with stage III 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 NG1 was considered well differentiated; NG2, moderately differentiated; and NG3, poorly differentiated. Based on 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 = 0.17). In multivariate analyses, size remained significant even when NG was present in the equation (p = 0.013). 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 NG1 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.

Notes: We conducted a single-institution study to determine whether local therapy plus six cycles of chemotherapy with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) followed by 5 years of tamoxifen is superior to local treatment alone in terms of disease-free survival (DFS) and overall survival (OS) in patients with stage IV breast cancer with no evidence of disease (stage IV-NED breast cancer). Patients with breast cancer were eligible if they had histologic proof of a locoregional or distant recurrence that had been curatively resected, irradiated, or both and had no other evidence of disease. Patients who had received prior anthracycline therapy were not eligible. All patients received six cycles of intravenous FAC, with cycles repeated every 3 weeks. After completion of chemotherapy, patients whose tumors had not previously demonstrated resistance to tamoxifen and had positive or unknown estrogen receptor status received tamoxifen 20 mg by mouth daily for 5 years. Patients in this study were compared with a historical control population (patients with stage IV-NED breast cancer who never received systemic therapy) as well as with the patients in two previously reported trials of chemotherapy for stage IV-NED disease. Forty-seven patients were registered, but only 45 were evaluable. There was a highly statistically significant difference ( p 〈 0.001) in OS and DFS among the four groups, with patients in our most recent study having the best OS and DFS at 3 years compared with the control group (84% vs. 55% and 66% vs. 11%, respectively). When patients in all four groups were analyzed together in search of prognostic factors, we found that patients whose primary tumors had negative axillary lymph nodes had a statistically significant improvement in OS and DFS (p 〈 0.01) compared with patients with positive axillary lymph nodes. No survival differences were found between patients with positive and those with negative hormone receptor status. This study demonstrates a benefit in terms of OS and DFS for patients with stage IV-NED breast cancer who receive doxorubicin-based adjuvant chemotherapy. The benefit was greater on patients with node-negative primary tumors. In patients with stage IV-NED disease, doxorubicin-based chemotherapy should be considered standard treatment after adequate local control is achieved.

Notes: Abstract: A comprehensive review of the literature from 1975 to 1995 was conducted. Reports were identified using the Cancerline and Medline databases. The chemical structure, estrogen agonist and antagonist activity, and in vitro studies were reviewed and compared with those of tamoxifes. Also, the antitumor activity in cell lines and animal models was highlighted. The mechanisms of action, metabolism, route of administration, dose scheduling, antitumor activity, and side effects of each agent were reviewed and compared with those for tamoxifen, where available. Several new antiestrogens are at various stages of development. They are divided into nonsteroidal and steroidal antiestrogens. Among the nonsteroidal antiestrogens are agents like toremifene and droloxifene. Both produce response rates, and both have toxicity profiles that are comparable to tamoxifen. In addition, toremifene can chemosensitize estrogen receptor-negative tumors, reverse multidrug resistance, and affect tamoxifen-resistant tumors. The short half-life of droloxifene results in minimal serum accumulation, and therefore it may be sequentially used with other systemic therapies to maximize cell kill. ICI 182,780, a steroidal antiestrogen, is well tolerated, active in tamoxifen-resistant tumors, and has a potential role in the preoperative management of advanced breast cancer. Other potential benefits of these and other agents are discussed. Pure antiestrogens have documented antibreast cancer activity that is in some instances more potent than tamoxifen. Some have activity in estrogen receptor-negative or tamoxifen-resistant tumors. Others may help to reverse chemotherapy resistance. In addition, the potential role of these antiestrogens in radioimaging and their effect on lipid metabolism is also being recognized.