CONTEXT Accurate prediction of who will (or won’t) have high probability of survival benefit from standard treatments is fundamental for individualized cancer treatment strategies. OBJECTIVE To develop a predictor of response and survival from chemotherapy for newly diagnosed invasive breast cancer. DESIGN Development of different predictive signatures for resistance and response to neoadjuvant chemotherapy (stratified according to estrogen receptor (ER) status) from gene expression microarrays of newly diagnosed breast cancer (310 patients). Then prediction of breast cancer treatment-sensitivity using the combination of signatures for: 1) sensitivity to endocrine therapy, 2) chemo-resistance, and 3) chemo-sensitivity. Independent validation (198 patients) and comparison with other reported genomic predictors of chemotherapy response. SETTING Prospective multicenter study to develop and test genomic predictors for neoadjuvant chemotherapy. PATIENTS Newly diagnosed HER2-negative breast cancer treated with chemotherapy containing sequential taxane and anthracycline-based regimens then endocrine therapy (if hormone receptor-positive). MAIN OUTCOME MEASURES Distant relapse-free survival (DRFS) if predicted treatment-sensitive and absolute risk reduction (ARR, difference in DRFS of the two predicted groups) at median follow-up (3 years), and their 95% confidence intervals (CI). RESULTS Patients in the independent validation cohort (99% clinical Stage II–III) who were predicted to be treatment-sensitive (28% of total) had DRFS of 92% (CI 85–100) and survival benefit compared to others (absolute risk reduction (ARR) 18%; CI 6–28). Predictions were accurate if breast cancer was ER-positive (30% predicted sensitive, DRFS 97%, CI 91–100; ARR 11%, CI 0.1–21) or ER-negative (26% predicted sensitive, DRFS 83%, CI 68–100; ARR 26%, CI 4–28), and were significant in multivariate analysis after adjusting for relevant clinical-pathologic characteristics. Other genomic predictors showed paradoxically worse survival if predicted to be responsive to chemotherapy. CONCLUSION A genomic predictor combining ER status, predicted chemo-resistance, predicted chemo-sensitivity, and predicted endocrine sensitivity accurately identified patients with survival benefit following taxane-anthracycline chemotherapy.

Marking nodes with biopsy-confirmed metastatic disease allows for selective removal and improves pathologic evaluation for residual nodal disease after chemotherapy.

To determine the long-term prognosis in each phenotypic subset of breast cancer related to residual cancer burden (RCB) after neoadjuvant chemotherapy alone, or with concurrent human epidermal growth factor receptor 2 (HER2)-targeted treatment. MethodsWe conducted a pathologic review to measure the continuous RCB index (wherein pathologic complete response has RCB = 0; residual disease is categorized into three predefined classes of RCB index [RCB-I, RCB-II, and RCB-III]), and yp-stage of residual disease. Patients were prospectively observed for survival. Three patient cohorts received paclitaxel (T) followed by fluorouracil, doxorubicin, and cyclophosphamide (T/FAC): original development cohort (T/FAC-1), validation cohort (T/FAC-2), and independent validation cohort (T/FAC-3). Another validation cohort received FAC chemotherapy only, and a fifth cohort received concurrent trastuzumab (H) with sequential paclitaxel and fluorouracil, epirubicin, and cyclophosphamide (FEC; H+T/FEC). Phenotypic subsets were defined by hormone receptor (HR) and HER2 status at diagnosis, classified as HR-positive/HER2-negative, HER2-positive (HR-negative/HER2-positive or HR-positive/HER2-positive), or triple receptor-negative. Relapse-free survival estimates were determined from Kaplan-Meier analysis and compared using the log-rank test. Results Five cohorts (T/FAC-1 [n = 219], T/FAC-2 [n = 262], T/FAC-3 [n = 342], FAC [n = 132], and H+T/FEC[n = 203]) had median event-free follow-up of 13.5, 9.1, 6.8, 16.4, and 7.1 years, respectively. Continuous RCB index was prognostic within each phenotypic subset, independent of other clinicalpathologic variables. RCB classes stratified prognostic risk overall, within each phenotypic subset, and within yp-stage categories. Estimates of 10-year relapse-free survival rates in the four RCB classes (pathologic complete response, RCB-I, RCB-II, and RCB-III) were 86%, 81%, 55%, and 23% for triple receptor-negative; 83%, 97%, 74%, and 52% for HR-positive/HER2-negative in the combined T/FAC cohorts; and 95%, 77%, 47%, and 21% in the H+T/FEC cohort. ConclusionRCB was prognostic for long-term survival after neoadjuvant chemotherapy in all three phenotypic subsets of breast cancer. Our institutional findings should be externally validated.

The goal of these guidelines, based on an expert consensus after careful review of published data, is to help the clinical diagnosis of this rare disease and to standardize management of IBC among treating physicians in both the academic and community settings.

Inflammatory breast cancer (IBC) is a rare and aggressive form of invasive breast cancer accounting for 2.5% of all breast cancer cases. It is characterized by rapid progression, local and distant metastases, younger age of onset, and lower overall survival compared with other breast cancers. Historically, IBC is a lethal disease with less than a 5% survival rate beyond 5 years when treated with surgery or radiation therapy. Because of its rarity, IBC is often misdiagnosed as mastitis or generalized dermatitis. This review examines IBC's unique clinical presentation, pathology, epidemiology, imaging, and biology and details current multidisciplinary management of the disease, which comprises systemic therapy, surgery, and radiation therapy. CA Cancer J Clin 2010;60:351-375.© 2010 American Cancer Society, Inc.To earn free CME credit or nursing contact hours for successfully completing the online quiz based on this article, go to http://CME.AmCancerSoc.org.Inflammatory breast cancer (IBC) is a clinicopathological entity characterized by rapid progression and aggressive behavior from onset of disease. Historically, its prognosis has been very grim. Especially before the introduction of systemic chemotherapy, attempts to control IBC with either surgery alone or surgery combined with radiation therapy resulted in median survival times of less than 15 months and local recurrence rates as high as 50%. 1 Although survival times have increased with multimodal therapy, they are still around 35% to 40% and much lower than those for other breast cancers. Because IBC is rare, clinicians are less familiar with it than with the more common types of noninflammatory breast cancers (non-IBC). The purpose of this review is to describe the clinical diagnosis, epidemiology, imaging, biology, and multidisciplinary treatment of IBC. We summarize both current practice and novel concepts under investigation.

BACKGROUND As women in the US delay childbearing, it has been hypothesized that the incidence of breast cancer diagnosed during pregnancy will increase. There are very little prospective data on the treatment of pregnant women with breast cancer with chemotherapy and even less data on the outcomes of their children who were exposed to chemotherapy in utero. METHODS Fifty‐seven pregnant breast cancer patients were treated on a single‐arm, multidisciplinary, institutional review board‐approved protocol with FAC (5‐fluorouracil, doxorubicin, cyclophosphamide) in the adjuvant (n = 32) or neoadjuvant (n = 25) setting. Parents/guardians were surveyed by mail or telephone regarding outcomes of children exposed to chemotherapy in utero. RESULTS Of the 57 women, 40 are alive and disease‐free, 3 have recurrent breast cancer, 12 died from breast cancer, 1 died from other causes, and 1 was lost to follow‐up. Of the 25 patients who received neoadjuvant FAC, 6 had a pathologic complete response, whereas 4 had no tumor response to chemotherapy and eventually died from their disease. All women who delivered had live births. One child has Down syndrome and 2 have congenital anomalies (club foot; congenital bilateral ureteral reflux). The children are healthy and those in school are doing well, although 2 have special educational needs. CONCLUSIONS Breast cancer can be treated with FAC chemotherapy during the second and third trimesters without significant short‐term complications for the majority of children exposed to chemotherapy in utero. Longer follow‐up of the children is needed to evaluate possible late side effects such as impaired cardiac function and fertility. Cancer 2006. © 2006 American Cancer Society.

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A mass that shows homogeneous or heterogeneous hyperechogenicity at US (with associated architectural distortion) and has a hypervascular, hemorrhagic, and heterogeneous appearance and typical malignant enhancement characteristics at MR imaging should alert the radiologist to a possible diagnosis of angiosarcoma.