Neoadjuvant chemotherapy has the capacity to completely clear the breast and axillary lymph nodes of invasive tumor before surgery. Patients with LABC who have a pCR in the breast and axillary nodes have a significantly improved disease-free survival rate. However, a pCR does not entirely eliminate recurrence. Further efforts should focus on elucidating the molecular mechanisms associated with this response.

This revised staging system will be officially adopted for use in tumor registries in January 2003.

Purpose The objective of this study was to determine whether the addition of trastuzumab to chemotherapy in the neoadjuvant setting could increase pathologic complete response (pCR) rate in patients with human epidermal growth factor receptor 2 (HER2) –positive disease. Patients and Methods Forty-two patients with HER2-positive disease with operable breast cancer were randomly assigned to either four cycles of paclitaxel followed by four cycles of fluorouracil, epirubicin, and cyclophosphamide or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks. The primary objective was to demonstrate a 20% improvement in pCR (assumed 21% to 41%) with the addition of trastuzumab to chemotherapy. The planned sample size was 164 patients. Results Prognostic factors were similar in the two groups. After 34 patients had completed therapy, the trial's Data Monitoring Committee stopped the trial because of superiority of trastuzumab plus chemotherapy. pCR rates were 25% and 66.7% for chemotherapy (n = 16) and trastuzumab plus chemotherapy (n = 18), respectively (P = .02). The decision was based on the calculation that, if study continued to 164 patients, there was a 95% probability that trastuzumab plus chemotherapy would be superior. Of the 42 randomized patients, 26% in the chemotherapy arm achieved pCR compared with 65.2% in the trastuzumab plus chemotherapy arm (P = .016). The safety of this approach is not established, although no clinical congestive heart failure was observed. A more than 10% decrease in the cardiac ejection fraction was observed in five and seven patients in the chemotherapy and trastuzumab plus chemotherapy arms, respectively. Conclusion Despite the small sample size, these data indicate that adding trastuzumab to chemotherapy, as used in this trial, significantly increased pCR without clinical congestive heart failure.

A 30-probe set pharmacogenomic predictor predicted pCR to T/FAC chemotherapy with high sensitivity and negative predictive value. This test correctly identified all but one of the patients who achieved pCR (12 of 13 patients) and all but one of those who were predicted to have residual disease had residual cancer (27 of 28 patients).

Monthly infusions of pamidronate as a supplement to chemotherapy can protect against skeletal complications in women with stage IV breast cancer who have osteolytic bone metastases.

BACKGROUND Pamidronate therapy previously has been shown to reduce skeletal complications effectively for up to 12 months in breast carcinoma patients with bone metastases. The current study data provide further follow‐up results regarding the effects of long term (up to 24 months) pamidronate treatment in women with breast carcinoma and osteolytic metastases. METHODS Follow‐up results from two prospective, multicenter, randomized, double‐blind, placebo‐controlled intervention trials conducted at academic and community oncology centers were combined to provide a large data set with which to evaluate the long term efficacy and safety of pamidronate therapy. Seven hundred fifty‐four women with Stage IV breast carcinoma and osteolytic metastases were randomized to the 2 treatment arms of the trial. Three patients were excluded from the intent‐to‐treat population for the analysis. A total of 751 evaluable patients were randomized to receive either a 90‐mg intravenous pamidronate infusion (367 patients) or a placebo infusion (384 patients) every 3–4 weeks. The primary outcome measures were skeletal morbidity rate (events/year), proportion of patients developing a skeletal complication, and time to first skeletal complication. RESULTS Of the 367 women receiving pamidronate, 115 (31.3%) completed the trial and 81 (22.1%) discontinued the study due to adverse events. Of the 384 women who received placebo, 100 (26.0%) completed the study and 76 (19.8%) discontinued the study due to adverse events. The skeletal morbidity rate was 2.4 in the pamidronate group and 3.7 in the placebo group (P < 0.001). In the pamidronate group, 186 of the 367 patients (51%) had skeletal complications compared with 246 of the 384 patients in the placebo group (64%) (P < 0.001). The median time to first skeletal complication was 12.7 months in the pamidronate group and 7 months in the placebo group (P < 0.001). Six patients treated with pamidronate discontinued treatment due to drug‐related adverse events. Pain and analgesic scores were significantly worse in the placebo group compared with those patients in the pamidronate group. CONCLUSIONS In the current study, monthly infusions of 90 mg of pamidronate as a supplement to antineoplastic therapy were found to be well tolerated and superior to antineoplastic therapy alone in preventing skeletal complications and palliating symptoms for at least 24 months in breast carcinoma patients with osteolytic bone metastases. Cancer 2000;88:1082–90. © 2000 American Cancer Society.

Background We aimed to describe clinicopathological features, patterns of recurrence, and survival according to breast cancer subtype, with a focus on triple-negative tumors. Methods We evaluated 15,204 women presenting to NCCN centers with stage I-III breast cancer between January 2000 and December 2006. Tumors were classified as hormone receptor positive [HR+]/HER2− (ER+ and/or PR+, and HER2−), HER2+ (HER2+, any ER or PR), or triple-negative (ER−, PR−, and HER2−). Results Subtype distribution was: triple-negative 17% (n=2,569), HER2+ 17% (n=2,602), HR+/HER2− 66% (n=10,033). Triple-negative subtype was more frequent in African-Americans, compared with Caucasians (adjusted odds ratio [OR] 1.98; p<0.0001). Premenopausal, but not postmenopausal, women with high body mass index had an increased likelihood of triple negative subtype (p=0.02). Women with triple-negative cancers were less likely to present on the basis of an abnormal screening mammogram (29% vs. 48%, p<0.0001), more likely to present with higher T stage, but less likely to have nodal involvement. Relative to HR+/HER2− tumors, triple-negative tumors were associated with a higher risk of brain or lung metastases, and had worse breast cancer-specific and overall survival, even after adjusting for age, stage, race, grade, and receipt of adjuvant chemotherapy (adjusted hazard ratio [HR] for overall survival 2.72, 95% CI 2.39–3.10, p<0.0001). The difference in risk of death by subtype was most dramatic within the first two years after diagnosis (HR for OS for 0 to 2 yrs 6.10 [95% CI 4.81, 7.74]). Conclusions Triple-negative tumors are associated with unique risk factors and worse outcomes compared to HR+/HER2− tumors.

Treatment with 90 mg of pamidronate as a 2-hour intravenous infusion every 4 weeks in addition to hormonal therapy significantly reduces skeletal morbidity from osteolytic metastases.