taxane and Carcinoma--Lobular

This study was designed to determine (1) rates of clinically meaningful tumor reduction in breast tumor size following neoadjuvant chemotherapy (NAC), (2) which receptor subtypes and MRI phenotypes are associated with clinically meaningful tumor reduction, and (3) whether MRI phenotype impacts concordance between pathologic and MRI size.. We analyzed data from the I-SPY TRIAL, a multicenter, prospective NAC trial. Reduction in tumor size from >4 to ≤4 cm was considered clinically meaningful, as crossing this threshold was considered a reasonable cutoff for potential breast conservation therapy (BCT). MRI phenotypes were scored between one (well-defined) and five (diffuse) on pre-NAC MRIs.. Of 174 patients with tumors >4 cm, 141 (81%) had clinically meaningful tumor reduction. Response to therapy varied by MRI phenotype (p = 0.003), with well-defined phenotypes more likely than diffuse phenotypes to have clinically meaningful tumor shrinkage (91 vs. 72%, p = 0.037). Her2+ and triple-negative (Tneg) tumors had the highest rate of clinically meaningful tumor reduction (p = 0.005). The concordance between tumor diameter on MRI and surgical pathology was highest for Her2+ and Tneg tumors, especially among tumors with solid imaging phenotypes (p = 0.004).. NAC allows most patients with large breast tumors to have clinically meaningful tumor reduction, meaning response that would impact ability to undergo BCT. However, response varies by imaging and tumor subtypes. Concordance between tumor size on MRI and surgical pathology was higher in well-defined tumors, especially those with a Tneg subtype, and lower in HR+ diffuse tumors.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Cyclophosphamide; Doxorubicin; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Prospective Studies; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Taxoids; Trastuzumab

To investigate the impact of histologic type invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC) on response to primary chemotherapy (PC) and long-term outcome.. The study included 1,034 patients with stage II and III breast cancer who participated in six clinical trials of PC at our institution between 1985 and 2002. One hundred twenty-two patients (12%) had ILC and 912 (88%) had IDC. All patients received anthracycline-based PC, and 346 patients (33.5%) also received a taxane as part of PC. Pathologic complete response (pCR) was defined as no evidence of invasive disease in the breast and axillary lymph nodes.. The median patient age was 48 years (range, 18 to 79 years). Patients with ILC tended to be older (median age, 53 years v 47 years for patients with IDC) and have more hormone-receptor-positive tumors (92% v 62%; P < .001), lower nuclear grade (nuclear grade 3, 16% v 56%; P < .001), and higher stage at diagnosis (10% v 0% with stage IIIB or IIIC disease; P < .001). Patients with ILC were less likely to have a pCR (3% v 15%; P < .001) and had a larger number of involved axillary lymph nodes (41% v 26% had > 3 involved nodes; P = .001). At a median follow-up time of 70 months, ILC patients tended to have longer recurrence-free survival (P = .004) and overall survival (P = .001).. ILC is characterized by lower rates of pathologic response to PC but better long-term outcomes compared to IDC. pCR might not be a prognostic indicator for this group of patients.

Topics: Adolescent; Adult; Age Factors; Aged; Axilla; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal; Carcinoma, Lobular; Disease-Free Survival; Humans; Lymph Nodes; Middle Aged; Neoplasms, Hormone-Dependent; Taxoids; Treatment Outcome

Phase II study evaluating efficacy and safety of combined oxaliplatin/fluorouracil (5-FU) in taxane-pretreated advanced and metastatic breast cancer (ABC) patients.. Sixty-four taxane- and anthracycline-pretreated (within 6 months of study entry) women were treated with oxaliplatin 130 mg/m(2) (2-hour intravenous [IV] infusion), day 1, and 5-FU 1,000 mg/m(2)/d (continuous IV infusion) days 1 to 4, every 3 weeks.. Median patient age was 51 years (range, 34 to 71 years), with a median of two involved organs (range, one to six organs), and metastases in the liver (70%), bone (47%), and lung (34%). Patients had a median of two prior chemotherapy regimens (range, one to six regimens), and 78% had previous hormonal therapy, with clinical taxane and anthracycline resistance in 53% and 34%, respectively. A total of 367 cycles were administered, with a median of six cycles/patient (range, one to 15 cycles). Sixty patients were assessable for response (World Health Organization criteria): 17 partial response, 26 stable disease, and 17 disease progression, giving an overall response rate of 27% (95% confidence interval, 16.3% to 39.1%), and 26% and 36% in taxane- and anthracycline-resistant populations, respectively, all responders having metastatic liver disease. Median time to progression was 4.8 months, and median overall survival was 11.9 months. Four treatment-related serious adverse events occurred, seven patients withdrew because of treatment-related toxicity. Hematotoxicity was prevalent but rarely severe, with grade 3-4 neutropenia, leukopenia, and thrombocytopenia in 34%, 19%, and 16% of patients, respectively, and a single episode of febrile neutropenia. One third of patients developed grade 2-3 peripheral neuropathy (oxaliplatin-specific scale), with grade 3 in only 8%.. This oxaliplatin/5-FU combination is effective with an excellent safety profile in anthracycline/taxane-pretreated ABC patients, showing encouraging activity in patients with anthracycline/taxane-resistance or visceral disease.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Disease-Free Survival; Drug Resistance, Neoplasm; Female; Fluorouracil; Humans; Infusions, Intravenous; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Safety; Survival Rate; Taxoids; Treatment Outcome

Diffuse optical spectroscopy (DOS) has been demonstrated capable of monitoring response to neoadjuvant chemotherapy (NAC) in locally advanced breast cancer (LABC) patients. In this study, we evaluate texture features of pretreatment DOS functional maps for predicting LABC response to NAC.. Locally advanced breast cancer patients (n=37) underwent DOS breast imaging before starting NAC. Breast tissue parametric maps were constructed and texture analyses were performed based on grey-level co-occurrence matrices for feature extraction. Ground truth labels as responders (R) or non-responders (NR) were assigned to patients based on Miller-Payne pathological response criteria. The capability of DOS textural features computed on volumetric tumour data before the start of treatment (i.e., 'pretreatment') to predict patient responses to NAC was evaluated using a leave-one-out validation scheme at subject level. Data were analysed using a logistic regression, naive Bayes, and k-nearest neighbour classifiers.. This study demonstrated that the pretreatment DOS texture features can predict breast cancer response to NAC and potentially guide treatments.

Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Chemotherapy, Adjuvant; Female; Hemoglobins; Humans; Middle Aged; Neoadjuvant Therapy; Oxygen; Predictive Value of Tests; ROC Curve; Spectrum Analysis; Taxoids; Tomography, Optical; Trastuzumab; Tumor Burden

Locally advanced breast cancer (LABC) is a major problem, especially in developing countries. The standard treatment for LABC is neoadjuvant chemotherapy, with or without anti-Her2 therapy, followed by surgery, radiotherapy, and adjuvant systemic treatment if appropriate. However, there are few data in the literature addressing alternatives when neoadjuvant chemotherapy fails to reduce the tumour for surgery.. We conducted a retrospective study including all patients who had non-metastatic LABC treated with neoadjuvant chemotherapy and who were not eligible for surgical resection; these patients were submitted to salvage radiotherapy (RTX) between January 2000 and December 2012 at the Brazilian National Cancer Institute.. Fifty-seven patients were included, with a median age of 51 (23-72) years. The most frequent clinical stages were IIIA and IIIB, corresponding to 19.3% and 70.2%, respectively; mean tumour size was 8.74 (3-18) cm, and 44 patients (77.2%) had nodal involvement. Chemotherapeutic regimens containing anthracyclines were prescribed to 98.2% of the patients. Fifteen patients (26.3%) received taxanes and anthracyclines. Radiation dose was 50 Gy divided into 25 fractions; 43 patients (75.4%) had their tumours downsized by RTX and underwent mastectomy. Overall survival (OS) was 38 (23-52) months. Patients who were submitted to surgery had an OS of 49 (28-70) months and those who were not eligible for mastectomy after radiotherapy had an OS of 18 (9-27) months.. This retrospective study confirms that RTX is an effective treatment to downsize LABC tumours with low or no response to chemotherapy, thereby enabling surgical resection which may improve overall patient outcome.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Chemotherapy, Adjuvant; Disease-Free Survival; Dose Fractionation, Radiation; Female; Humans; Mastectomy; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Retrospective Studies; Salvage Therapy; Survival Rate; Taxoids; Tumor Burden; Young Adult

During the past decade, neoadjuvant chemotherapy (NAC) has been increasingly used in patients to reduce large tumors to a size eligible for breast-conserving therapy (BCT). However, the association between NAC and Ki-67 has not yet been fully elucidated. The aim of this study was to evaluate the prognostic significance of Ki-67, specifically after NAC followed by BCT, particularly in terms of locoregional recurrence (LRR).. A total 217 patients who received BCT after NAC were retrospectively analyzed. In these patients, immunohistochemistry analyses defined four tumor subtypes, Luminal A, Luminal B, Triple negative, and HER2 type. Ki-67 was examined by immunohistochemistry in both pretreatment core needle samples and post-treatment surgical excision specimens. High Ki-67 expression was defined as >20%. The prognostic factors LRR, locoregional relapse-free survival (LRRFS), and overall survival (OS) were analyzed.. In total, LRR developed in 14 patients, and the 5 year-LRRFS was 94.2%. Post-treatment high Ki-67 expression, triple negative, the presence of lymphovascular invasion, and histological grade 3 were significantly high in LRR for prognostic factors (P < 0.05). There were significant differences in Kaplan-Meier method for LRRFS curves according to these three factors for patients receiving BCT following NAC (P < 0.05). There was a significant difference in the 5 year-OS for patients with and without LRR (41.7% vs. 93.9%, P < 0.001).. Post-treatment high Ki-67 expression could be one of the important prognostic factors of LRR, and require careful follow-up on LRR at the time of surveillance.

Topics: Adult; Aged; Anthracyclines; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Female; Humans; Ki-67 Antigen; Lymph Node Excision; Mastectomy, Segmental; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Prognosis; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Taxoids; Trastuzumab

PURPOSE Although most breast cancer patients who receive neoadjuvant chemotherapy (NCT) have a tumor response, a small proportion experience progressive disease (PD). Predictors of response have been reported, but predictors for progression have not been identified. We sought to identify predictors of tumor progression during NCT with the ultimate aim of identifying patients who might benefit from a first-line surgical approach or from novel targeted therapies. PATIENTS AND METHODS Data were obtained from reviewing medical records of patients with stage I to III breast cancer who received NCT (anthracycline and/or taxane based). Statistical analysis was performed to compare patients with any response or stable disease with patients with PD. RESULTS One thousand nine hundred twenty-eight patients received NCT; 1,762 patients (91%) had some response, 107 (6%) had stable disease, and 59 (3%) had PD at some point during NCT. Factors predictive of PD included African American race (P = .002), tumor (T) status (P = .002), and American Joint Committee on Cancer clinical stage (P = .02). Histopathologic features of PD were high tumor grade (P = .005), high Ki-67 score (P = .002), and negative estrogen receptor (ER)/progesterone receptor (PR) status (P < .001/P < .001). Pre-NCT T status, race, and ER status were independent predictors of progression in multivariate analysis. Disease progression was a negative predictor of distant disease-free survival and overall survival in multivariate analysis (P < .001). CONCLUSION Factors predictive of PD include race, advanced tumor stage, high nuclear grade, high Ki-67 score, and ER/PR negativity. Because many of these variables are also associated with response to NCT, novel molecular predictors are needed to identify patients at risk for progression on standard NCT.

Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Chemotherapy, Adjuvant; Disease Progression; Female; Humans; Middle Aged; Neoadjuvant Therapy; Receptors, Estrogen; Receptors, Progesterone; Survival Rate; Taxoids; Treatment Outcome; Young Adult

It is accepted that preoperative chemotherapy can result in increased breast preservation for breast cancers greater than 4 cm. The benefits of preoperative chemotherapy are less clear, however, for patients who present with smaller tumors and are already candidates for breast-preserving surgery. The goal of this study is to assess the effect of preoperative chemotherapy on breast cancers between 2 and 4 cm diameter.. A retrospective chart review was conducted of patients diagnosed with new breast cancer at the Yale-New Haven Breast Center for the years 2002-2007. Patients were included in the study if their breast cancer was between 2 and 4 cm and their initial surgical treatment had been completed. Patients with distant metastases were excluded.. There were 156 new cancers that met study requirements. Forty-seven patients underwent preoperative chemotherapy, and 109 patients had their surgery first, usually followed by chemotherapy. Initial surgery was lumpectomy for 31 out of 47 patients (66%) in the preoperative chemotherapy group compared with 62 out of 109 patients (57%) in the surgery group. For patients with lumpectomies, 2 out of 31 patients (6%) in the preoperative group had positive margins and required re-excision compared with 20 out of 62 patients (37%) in the surgery-first group (P<0.01).. We conclude that, for tumors between 2 and 4 cm, preoperative chemotherapy is associated with a significantly decreased rate of re-excision following lumpectomy. This not only results in fewer mastectomies, but also avoids the morbidity and inferior cosmetic results associated with a re-excision lumpectomy.

Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Lymph Nodes; Lymphatic Metastasis; Mastectomy; Mastectomy, Segmental; Middle Aged; Neoplasm Staging; Preoperative Care; Prognosis; Prospective Studies; Retrospective Studies; Risk Factors; Survival Rate; Taxoids; Treatment Outcome