Carcinoma en cuirasse.

Carcinoma en cuirasse (CeC) is an extremely rare form of cutaneous metastasis of breast cancer. Guidelines for diagnosis and treatment of CeC are limited due to the small number of reported cases. It can be difficult to distinguish CeC from benign etiologies on initial presentation, but CeC can be easily distinguished by histopathology. Treatment of CeC focuses on palliation with no consensus on therapy guidelines. Treatment modalities that have been explored include chemotherapy, radiotherapy (with or without local hyperthermia), and hormonal antagonists. Here we present a 62-year-old woman with recurrent triple-negative breast cancer manifesting as CeC to the chest wall.

Clinico-radiologic features and management of hematological tumors in the breast: a case series.

Hematological tumors arising in the breast are uncommon and require different treatment modalities dependent upon tumor type. Current treatment options include surgical excision, chemotherapy, and radiotherapy. Management of these breast malignancies are poorly outlined in the literature. The purpose of this case series is to report five cases consisting of extranodal marginal zone lymphoma, lymphoplasmacytic lymphoma, and extramedullary plasmacytoma occurring in the breast. The cases illustrate heterogeneous radiologic findings and varying management approaches to these tumors. The case series underscores the importance of having a wide differential at diagnosis and recognizes management of disease should be taken on an individual basis with consideration of prognosis and first-line treatment options.

Five-year results of a phase II trial of preoperative 5-fluorouracil, epirubicin, cyclophosphamide followed by docetaxel with capecitabine (wTX) (with trastuzumab in HER2-positive patients) for patients with stage II or III breast cancer.

We aimed to increase pathologic complete response (pCR) in patients with invasive breast cancer by adding preoperative capecitabine to docetaxel following 5-fluorouracil, epirubicin, cyclophosphamide (FEC) (with trastuzumab for patients with HER2-positive disease) and to evaluate 5-year disease-free survival (DFS) associated with this preoperative regimen. Chemotherapy included four cycles of FEC100 (5-fluorouracil 500 mg/m2 , epirubicin 100 mg/m2 , cyclophosphamide 500 mg/m2 IV on Day 1 every 21 days) followed by 4 21-day cycles of docetaxel (35 mg/m2  days 1 and 8) concurrently with capecitabine (825 mg/m2 orally twice daily for 14 days followed by 7 days off) (wTX). For HER2-positive patients, treatment was modified by decreasing epirubicin to 75 mg/m2 and adding trastuzumab (H) in standard doses (FEC75-H →wTX-H). The study objective was to achieve a pCR rate in the breast and axillary lymph nodes of 37% in patients with HER2-negative breast cancer and of 67% in patients with HER2-positive breast cancer treated with preoperative trastuzumab. A total of 186 patients were enrolled on study. In an intent-to-treat analysis, the pCR rate was 31% (37/118, 95% CI: 24-40%) in the HER2-negative patients, 24% (15/62, 95% CI: 14-37%) in ER-positive/HER2-negative patients, 39% (22/56, 95% CI: 27-53%) in the ER-negative/HER2-negative patients, and 46% (29/63, 95% CI: 34-48%) in the HER2-positive patients. The pCR rate in the 40 trastuzumab-treated patients was 53% (21/40, 95% CI: 38-67%). Grade 3 and 4 adverse events included neutropenia, leukopenia, diarrhea, and hand-foot skin reactions. One trastuzumab-treated patient developed grade 3 cardiotoxicity, and 4 others experienced grade 1-2 decrements in left ventricular function; all five patients' cardiac function returned to their baseline upon completion of trastuzumab. At 5 years, disease-free survival was 70% in the HER2-negative population (78% in ER-positive/HER2-negative and 62% in the ER-negative/HER2-negative patients) and 80% in the HER2-positive patients (87% in the trastuzumab-treated HER2-positive patients). At 5 years, overall survival was 80% in the HER2-negative population (88% in ER-positive/HER2-negative and 71% in the ER-negative/HER2-negative patients) and 86% in the HER2-positive patients (94.5% in the trastuzumab-treated HER2-positive patients). FEC100 (FEC75 with trastuzumab) followed by weekly docetaxel plus capecitabine, with or without trastuzumab is a safe, effective preoperative cytotoxic regimen. However, the addition of capecitabine to docetaxel following FEC, with or without trastuzumab, did not increase pCR rates nor 5-year DFS over the rates that have been reported with standard preoperative doxorubicin/cyclophosphamide (AC) followed by paclitaxel, with or without trastuzumab. Therefore, the use of capecitabine as part of preoperative chemotherapy is not recommended.

Two cancers in one: breast carcinoma with underlying melanoma.

A 61-year-old woman presented with a diagnosis of metastatic invasive lobular carcinoma of the right breast, and after treatment it had regressed or was stable except for a scalp nodule. When biopsied, the outer edges of the scalp lesion had findings consistent with breast carcinoma; however, the bulk of the tumor's pathology was consistent with melanoma. It appeared that most of the tumor was a highly vascularized melanoma with lobular breast carcinoma noted at its edges.

Our experience as a Health Volunteers Overseas-sponsored team in Huê´, Vietnam.

A group from Texas Oncology and Baylor Charles A. Sammons Cancer Center traveled to Huê´, Vietnam, as part of Health Volunteers Overseas. From February 21 to March 6, 2012, five Baylor Sammons medical oncologists and an oncology nurse worked with a medical oncologist and a surgeon at the Huê´ College of Medicine and Pharmacy, suggesting approaches based on available resources. The two groups worked together to find optimal solutions for the patients. What stood out the most for the Baylor Sammons group was the Huê´ team's remarkable work ethic, empathy for patients, and treatment resourcefulness. The Baylor Sammons group also identified several unmet needs that could potentially be addressed by future volunteers in Huê´, including creation of an outpatient hospice program, establishment of breast cancer screening, modernization of the pathology department, instruction in and better utilization of pain management, better use of clinic space, and the teaching of oncology and English to medical students. There was a mutual exchange of knowledge between the two medical teams. The Baylor Sammons group not only taught but also learned how to take good care of patients with limited resources.

Iniparib plus chemotherapy in metastatic triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancers have inherent defects in DNA repair, making this cancer a rational target for therapy based on poly(adenosine diphosphate-ribose) polymerase (PARP) inhibition. METHODS: We conducted an open-label, phase 2 study to compare the efficacy and safety of gemcitabine and carboplatin with or without iniparib, a small molecule with PARP-inhibitory activity, in patients with metastatic triple-negative breast cancer. A total of 123 patients were randomly assigned to receive gemcitabine (1000 mg per square meter of body-surface area) and carboplatin (at a dose equivalent to an area under the concentration-time curve of 2) on days 1 and 8--with or without iniparib (at a dose of 5.6 mg per kilogram of body weight) on days 1, 4, 8, and 11--every 21 days. Primary end points were the rate of clinical benefit (i.e., the rate of objective response [complete or partial response] plus the rate of stable disease for ≥6 months) and safety. Additional end points included the rate of objective response, progression-free survival, and overall survival. RESULTS: The addition of iniparib to gemcitabine and carboplatin improved the rate of clinical benefit from 34% to 56% (P=0.01) and the rate of overall response from 32% to 52% (P=0.02). The addition of iniparib also prolonged the median progression-free survival from 3.6 months to 5.9 months (hazard ratio for progression, 0.59; P=0.01) and the median overall survival from 7.7 months to 12.3 months (hazard ratio for death, 0.57; P=0.01). The most frequent grade 3 or 4 adverse events in either treatment group included neutropenia, thrombocytopenia, anemia, fatigue or asthenia, leukopenia, and increased alanine aminotransferase level. No significant difference was seen between the two groups in the rate of adverse events. CONCLUSIONS: The addition of iniparib to chemotherapy improved the clinical benefit and survival of patients with metastatic triple-negative breast cancer without significantly increased toxic effects. On the basis of these results, a phase 3 trial adequately powered to evaluate overall survival and progression-free survival is being conducted. (Funded by BiPar Sciences [now owned by Sanofi-Aventis]; ClinicalTrials.gov number, NCT00540358.).

Independent adjudication of symptomatic heart failure with the use of doxorubicin and cyclophosphamide followed by trastuzumab adjuvant therapy: a combined review of cardiac data from the National Surgical Adjuvant breast and Bowel Project B-31 and the North Central Cancer Treatment Group N9831 clinical trials.

PURPOSE: An independent Adjuvant Cardiac Review and Evaluation Committee (ACREC) systematically reviewed cases of symptomatic heart failure events to uniformly define the cardiac event rate across two large trials (National Surgical Adjuvant Breast and Bowel Project [NSABP] B-31 and North Central Cancer Treatment Group [NCCTG] N9831) that assessed the addition of trastuzumab to standard adjuvant chemotherapy. PATIENTS AND METHODS: The committee was composed of six independent oncologists and cardiologists. A retrospective review of patients with a cardiac event was performed by the primary investigators of the trials. The ACREC prospectively established criteria for determining a symptomatic heart failure event. Recovery status was determined from documented resolution of signs and symptoms. Potential risk factors were also assessed. RESULTS: Medical records for a total of 173 patients were reviewed: 40 in the chemotherapy-alone arm and 133 in the trastuzumab arm. Trastuzumab-treated patients had a 2.0% incidence of symptomatic heart failure events compared with 0.45% in the chemotherapy-alone arm. Complete or partial recovery was observed in 86.1% of trastuzumab-treated patients with symptomatic heart failure events. Of five patients who died, only one patient had received trastuzumab. Independent predictors for cardiac events were age older than 50 years, a low ejection fraction at the start of paclitaxel treatment, and trastuzumab treatment. CONCLUSION: The incidence of symptomatic heart failure events is 2.0% in patients treated with adjuvant trastuzumab, and the majority of these patients recover with appropriate treatment.

Docetaxel With Cyclophosphamide Is Associated With an Overall Survival Benefit Compared With Doxorubicin and Cyclophosphamide: 7-Year Follow-Up of US Oncology Research Trial 9735.

PURPOSE: We previously reported that four cycles of docetaxel/cyclophosphamide (TC) produced superior disease-free survival (DFS) compared with four cycles of doxorubicin/cyclophosphamide (AC) in early breast cancer. Older women are under-represented in adjuvant chemotherapy trials. In our trial 16% of patients were > or = 65 years. We now report 7-year results for DFS and overall survival (OS) as well as the impact of age, hormone receptor status, and HER2 status on outcome and toxicity. PATIENTS AND METHODS: Patients were randomly assigned to receive either four cycles of standard-dose AC (60/600 mg/m(2); n = 510), or TC (75/600 mg/m(2); n = 506), administered by intravenous infusion every 3 weeks. RESULTS: The median age in women younger than 65, was 50 years (range, 27 to 64) and for women > or = 65 was 69 years (range, 65 to 77). Baseline characteristics in the two age subgroups were generally well matched, except that older women tended to have more lymph node involvement. At a median of 7 years follow-up, the difference in DFS between TC and AC was significant (81% TC v 75% AC; P = .033; hazard ratio [HR], 0.74; 95% CI 0.56 to 0.98) as was OS (87% TC v 82% AC; P = .032; HR, 0.69; 95% CI, 0.50 to 0.97). TC was superior in older patients as well as younger patients. There was no interaction of hormone-receptor status or HER-2 status and treatment. Older women experienced more febrile neutropenia with TC and more anemia with AC. CONCLUSION: With longer follow-up, four cycles of TC was superior to standard AC (DFS and OS) and was a tolerable regimen in both older and younger patients.

Determination of oestrogen-receptor status and ERBB2 status of breast carcinoma: a gene-expression profiling study.

BACKGROUND: Gene expression microarrays are being used to develop new prognostic and predictive tests for breast cancer, and might be used at the same time to confirm oestrogen-receptor status and ERBB2 status. Our goal was to establish a new method to assign oestrogen receptor and ERBB2-receptor status to breast carcinoma based on mRNA expression measured using Affymetrix U133A gene-expression profiling. METHODS: We used gene expression data of 495 breast cancer samples to assess the correlation between oestrogen receptor (ESR1) and ERBB2 mRNA and clinical status of these genes (as established by immunohistochemical [IHC] or fluorescence in-situ hybridisation [FISH], or both). Data from 195 fine-needle aspiration (FNA) samples were used to define mRNA cutoff values that assign receptor status. We assessed the accuracy of these cutoffs in two independent datasets: 123 FNA samples and 177 tissue samples (ie, resected or core-needle biopsied tissues). Profiling was done at two institutions by use of the same platform (Affymetrix U133A GeneChip). All data were uniformly normalised with dCHIP software. FINDINGS: ESR1 and ERBB2 mRNA levels correlated closely with routine measurements for receptor status in all three datasets. Spearman's correlation coefficients ranged from 0.62 to 0.77. An ESR1 mRNA cutoff value of 500 identified oestrogen-receptor-positive status with an overall accuracy of 90% (training set), 88% (first validation set), and 96% (second validation set). An ERBB2 mRNA threshold of 1150 identified ERBB2-positive status with the overall accuracy of 93% (training set), 89% (first validation set), and 90% (second validation set). Reproducibility of mRNA measurements in 34 replicate experiments was high (correlation coefficient 0.975 for ESR1, 0.984 for ERBB2). INTERPRETATION: Amounts of ESR1 and ERBB2 mRNA as measured by the Affymetrix GeneChip reliably and reproducibly establish oestrogen-receptor status and ERBB2 status, respectively.

Phase II study of weekly albumin-bound paclitaxel for patients with metastatic breast cancer heavily pretreated with taxanes.

PURPOSE: Nanoparticle albumin-bound paclitaxel, a solvent-free, albumin-bound paclitaxel, demonstrated antitumor activity in patients with taxane-naive metastatic breast cancer (MBC). We examined albumin-bound paclitaxel (100 mg/m2 or 125 mg/m2 administered weekly) to determine the antitumor activity in patients with MBC whose disease progressed despite conventional taxane therapy. PATIENTS AND METHODS: Women with MBC that was previously treated with taxanes were eligible for participation. Taxane failure was defined as metastatic disease progression during taxane therapy or relapse within 12 months of adjuvant taxane therapy. Primary objectives were response rates (RRs) and the safety/tolerability of albumin-bound paclitaxel. RESULTS: Women were treated with albumin-bound paclitaxel 100 mg/m2 (n = 106) or 125 mg/m2 (n = 75) on days 1, 8, and 15 of a 28-day cycle. Response rates were 14% and 16% for the 100-mg/m2 and 125-mg/m2 cohorts, respectively; an additional 12% and 21% of patients, respectively, had stable disease (SD) > or = 16 weeks. Median progression-free survival times were 3 months at 100 mg/m2 and 3.5 months at 125 mg/m2; median survival times were 9.2 months and 9.1 months, respectively. Survival was similar for responding patients and those with SD. No severe hypersensitivity reactions were reported. Patients who developed treatment-limiting peripheral neuropathy typically could be restarted on a reduced dose of albumin-bound paclitaxel after a 1-2-week delay. Grade 4 neutropenia occurred in < 5% of patients. CONCLUSION: Albumin-bound paclitaxel 100 mg/m2 given weekly demonstrated the same antitumor activity as albumin-bound paclitaxel 125 mg/m2 weekly and a more favorable safety profile in patients with MBC that had progressed with previous taxane therapy. Survival of patients with SD > or = 16 weeks was similar to that of responders.

Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer.

PURPOSE: The combination of doxorubicin and cyclophosphamide (AC) is a standard adjuvant chemotherapy regimen. Studies of docetaxel and cyclophosphamide (TC) in metastatic breast cancer (MBC) showed promise in MBC. In 1997, we initiated a randomized adjuvant trial of TC compared with standard-dose AC with a primary end point of disease-free survival (DFS). PATIENTS AND METHODS: Patients were eligible if they had stage I to III operable invasive breast cancer with complete surgical excision of the primary tumor. Between June 1997 and December 1999, 1,016 patients were randomly assigned to four cycles of either standard-dose AC (60 and 600 mg/m2, respectively; n = 510) or TC (75 and 600 mg/m2, respectively; n = 506), administered intravenously every 3 weeks as adjuvant chemotherapy. Radiation therapy (as indicated) and tamoxifen, for patients with hormone receptor-positive disease, were administered after completion of chemotherapy. RESULTS: Both treatment groups (TC and AC) were well balanced with respect to major prognostic factors. Patients were observed through 2005 for a median of 5.5 years. At 5 years, DFS rate was significantly superior for TC compared with AC (86% v 80%, respectively; hazard ratio [HR] = 0.67; 95% CI, 0.50 to 0.94; P = .015). Overall survival rates for TC and AC were 90% and 87%, respectively (HR = 0.76; 95% CI, 0.52 to 1.1; P = .13). More myalgia, arthralgia, edema, and febrile neutropenia occurred on the TC arm; more nausea and vomiting occurred on the AC arm as well as one incident of congestive heart failure. CONCLUSION: At 5 years, TC was associated with a superior DFS and a different toxicity profile compared with AC.

Phase II study of trastuzumab plus gemcitabine in chemotherapy-pretreated patients with metastatic breast cancer.

We evaluated the efficacy and toxicity of trastuzumab plus gemcitabine in patients with HER2-positive metastatic breast cancer (MBC). Sixty-four patients were enrolled, the majority of whom (95%) had been treated with an anthracycline and a taxane before study enrollment. Eligible women were treated with gemcitabine (1200 mg/m(2) weekly for 2 weeks with the third week off on a 21-day cycle) plus weekly doses of trastuzumab (4-mg/kg loading dose; 2 mg/kg thereafter) until disease progression. The median patient age was 55 years, and the median number of previously administered (including adjuvant) chemotherapy regimens was 3. Twenty-two patients were scored as 2+ for HER2 expression by immunohistochemistry; 39 patients scored 3+. Three patients were assessed as HER2-negative on central pathology review and were ineligible for evaluation. Fifty-nine of the 61 patients remained evaluable for response. The objective response rates were 38% in the intent-to-treat population (23 of 61) and 44% among the 39 patients with HER2 3+ expression. The median response duration was 5.8 months, median overall survival was 14.7 months, and median time to disease progression was 5.8 months. Trastuzumab plus gemcitabine was well tolerated. No cases of clinical congestive heart failure occurred. Grade 3/4 toxicities included asthenia in 4 patients, fever in 4, neutropenia in 18, dyspnea in 6, abdominal or back pain in 3, and edema and nausea in 1 patient each. The combination of trastuzumab plus gemcitabine appears to be well tolerated and effective for patients with HER2-positive MBC previously treated with chemotherapy.

Phase II, randomized, double-blind study of two dose levels of arzoxifene in patients with locally advanced or metastatic breast cancer.

PURPOSE: To select a daily dose of arzoxifene (LY353381), a selective estrogen receptor modulator, for use in future studies in women with locally advanced or metastatic breast cancer who are either potentially tamoxifen sensitive (TS) or tamoxifen refractory (TR). PATIENTS AND METHODS: This trial was a randomized, double-blind, phase II study of arzoxifene 20 mg (n = 55) and 50 mg (n = 57) in women with advanced or metastatic breast cancer. Patients were randomly assigned to balance for number of metastatic disease sites, prior tamoxifen therapy, and estrogen receptor status. The primary end point was tumor response rate (RR). Secondary end points included clinical benefit rate (CBR), time to progression (TTP), and toxicity. RESULTS: Forty-nine patients were TS and 63 were TR. According to independent review, among TS patients, RR was higher in the 20-mg arm than the 50-mg arm (26.1% v 8.0%), with a longer TTP (8.3 v 3.2 months; P >.05). Among the TR patients, response rate was the same in the 20-mg and 50-mg arms (10.3%) with similar TTP (2.7 and 2.8 months, respectively; P >.05). CBR was higher in the 20-mg arm than in the 50-mg arm among TS patients (39.1% v 20.0%) and TR patients (13.8% v 10.3%). Arzoxifene was well tolerated. Dose-dependent toxicity was not demonstrated. There were no deaths during study. CONCLUSION: Arzoxifene is effective in the treatment of TS and TR patients with advanced or metastatic breast cancer at the 20-mg and 50-mg dose levels. Toxicities are minimal, and the therapy is tolerated. The 20-mg dose seems to be at least as effective as the 50-mg dose. Accordingly, arzoxifene 20 mg/d was selected for further study in patients with breast cancer.