taxane and Carcinoma--Ductal--Breast

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A healthy 56-year-old postmenopausal woman discovered a palpable mass at the one o'clock position of the left breast. After an initial biopsy confirmed breast cancer, she underwent mastectomy and axillary node dissection for a left-sided breast cancer that measured 3.5 cm. There was extensive lymphovascular invasion. Pathology review indicated a poorly differentiated, grade 3 invasive ductal carcinoma and ductal carcinoma in situ (largest focus, 3.5 cm). The margins were negative. Two of the 11 axillary lymph nodes contained metastatic carcinoma. Immunohistochemical studies previously obtained on the core biopsy indicated that the tumor was positive for estrogen receptor expression (50%), negative for progesterone receptor expression, and had a Ki-67 score of 60%. There was no amplification of the human epidermal growth factor receptor 2/ neu gene. Staging scans were negative for metastatic disease. Our multidisciplinary tumor board recommended adjuvant chemotherapy, postmastectomy radiation therapy, and endocrine therapy. A 52-year-old postmenopausal woman presented with a palpable mass of the right breast. An initial core biopsy confirmed carcinoma in the breast. She underwent quadrantectomy and axillary node dissection. The final pathology report disclosed a moderately differentiated invasive ductal carcinoma (diameter, 2.5 cm). The margins were negative. None of the three sentinel lymph nodes contained metastatic carcinoma. Immunohistochemical studies showed that the tumor was positive for estrogen receptor expression (90%) and for progesterone receptor expression (40%) and had a Ki-67 score of 20%. There was no amplification of the human epidermal growth factor receptor 2/ neu gene. Staging scans were negative for metastatic disease. A genomic assay was obtained and suggested an intermediate to high risk of recurrence. Her past medical history was notable for hypertension and moderately overweight status (body mass index, 39 kg/m

Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Axilla; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Chemotherapy, Adjuvant; Female; Humans; Lymph Node Excision; Lymphatic Metastasis; Mastectomy; Middle Aged; Neoplasm Invasiveness; Radiotherapy, Adjuvant; Taxoids

Purpose Docetaxel and cyclophosphamide (TC) was superior to doxorubicin and cyclophosphamide (AC) in a trial in early breast cancer. However, activity of TC relative to AC regimens with a taxane (TaxAC) is unknown. Methods In a series of three adjuvant trials, women were randomly assigned to TC for six cycles (TC6) or to a standard TaxAC regimen. US Oncology Research (USOR) 06-090 compared TC6 with docetaxel, doxorubicin, and cyclophosphamide (TAC6). National Surgical Adjuvant Breast and Bowel Project (NSABP) B-46-I/USOR 07132 compared TC6, TAC6, or TC6 plus bevacizumab. NSABP B-49 compared TC6 with several standard AC and taxane combination regimens. Before any analysis of individual trials, a joint efficacy analysis of TC versus the TaxAC regimens was planned, with invasive disease-free survival (IDFS) as the primary end point. Patients who received TC6 plus bevacizumab on NSABP B-46-I/USOR 07132 were not included. A hazard ratio (HR) from a stratified Cox model that exceeded 1.18 for TC6 versus TaxAC was predefined as inferiority for TC6. The prespecified interim monitoring plan was to report for futility if the HR was > 1.18 when 334 IDFS events were observed (50% of 668 events required for definitive analysis). Results A total of 2,125 patients were randomly assigned to receive TC6 regimens and 2,117 patients were randomly assigned to receive TaxAC regimens. The median follow-up time was 3.3 years. There were 334 IDFS events, and the HR for TC6 versus TaxAC was 1.202 (95% CI, 0.97 to 1.49), which triggered early reporting for futility. The 4-year IDFS was 88.2% for TC6 and was 90.7% for TaxAC ( P = .04). Tests for treatment interaction by protocol, hormone receptor status, and nodal status were negative. Conclusion The TaxAC regimens improved IDFS in patients with high-risk human epidermal growth factor receptor 2-negative breast cancer compared with the TC6 regimen.

Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Chemotherapy, Adjuvant; Cyclophosphamide; Disease-Free Survival; Docetaxel; Doxorubicin; Female; Follow-Up Studies; Humans; Lymphatic Metastasis; Mastectomy; Middle Aged; Prospective Studies; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Taxoids

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

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

We studied the effect of neoadjuvant chemotherapy (NAC) ± trastuzumab on the ductal carcinoma in situ (DCIS) component in patients with locally advanced breast cancer who achieved pathological complete response (pCR).. The diagnostic biopsies of 92 consecutive breast cancer patients that were treated with neoadjuvant chemotherapy (NAC) ± trastuzumab were evaluated for the presence of DCIS. Upon completion of NAC, the surgical specimens were evaluated for complete eradication of both the invasive and non-invasive cancer in the breast. The pretreatment mammograms were evaluated for the presence of microcalcifications and compared to the mammograms that were obtained upon completion of therapy prior to surgery.. Thirty of 92 patients (33%) had a substantial component of DCIS in the pretreatment biopsy. Thirty nine patients (42%) achieved pCR: 22 (56%) following NAC + trastuzumab, 17 (32%) following chemotherapy only. Ten of 30 patients (33%) with DCIS component achieved pCR: 4 received chemotherapy only, in 6 trastuzumab was added. Multiple microcalcifications on the pretreatment mammograms were observed in 3 of 10 patients with DCIS who achieved pCR. No reduction in the area of calcifications was observed following NAC.. DCIS may be completely eradicated by NAC ± trastuzumab. However, associated microcalcifications probably persist. Patients with locally advanced breast cancer with substantial DCIS may still opt for NAC and breast conservation as the DCIS component may respond and even completely disappear following NAC. Residual widespread microcalcifications after NAC do not necessarily indicate residual cancer. Larger studies are needed to direct the surgical management of these patients.

Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma in Situ; Carcinoma, Ductal, Breast; Female; Humans; Mammography; Middle Aged; Neoadjuvant Therapy; Prospective Studies; Taxoids; Trastuzumab; Treatment Outcome

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

Bone morphogenetic protein receptor type IB (BMPRIB) is one osteogenesis factor, which function in breast cancer has been rarely explored until recently. In the clinical study presented here, involving a cohort of 368 invasive ductal carcinoma (IDC) patients, we identified that patients with low expression of BMPRIB exhibited poor prognosis, especially in the luminal B subtype. We also provided the first piece of evidence that low level of BMPRIB was a promoting factor for breast cancer patients to develop bone metastasis, but not lung, liver or brain. The first of its kind, we reported that patients with high expression of BMPRIB exhibited favorable prognosis by a retrospective analysis consisting of 168 patients treated with TE (taxane and anthracycline) regimens. And the patients with high expression of BMPRIB were more sensitive to TE regimens in the detection of 32 paired pre-neoadjuvant and post-neoadjuvant specimens. Overall, our study concluded that low expression of BMPRIB indicated poor prognosis of breast cancer and was insensitive to taxane-anthracycline chemotherapy. Our findings also lay a foundation to help clinicians improve identification of patients for TE regimens by BMPRIB in the era of precision medicine.

Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bone Morphogenetic Protein Receptors, Type I; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Lymphatic Metastasis; Middle Aged; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Staging; Prognosis; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Retrospective Studies; Survival Rate; Taxoids

We previously reported survival trends among patients with inflammatory breast cancer (IBC) over a 30-year period before 2005. Here we evaluated survival outcomes for women with IBC diagnosed before or after October 2006, in the era of HER2-directed therapy and after opening a dedicated multidisciplinary IBC clinic.. We retrospectively identified and reviewed 260 patients with newly diagnosed IBC without distant metastasis, 168 treated before October 2006 and 92 treated afterward. Most patients received anthracycline and taxane-based neoadjuvant chemotherapy, mastectomy, and postmastectomy radiation. Survival outcomes were compared between the 2 groups.. Median follow-up time was 29 months for the entire cohort (39 and 24 mo for patients treated before and after October 2006). Patients treated more recently were more likely to have received neoadjuvant HER2-directed therapy for HER2-positive tumors (100% vs. 54%, P=0.001). No differences were found in receipt of hormone therapy. Three-year overall survival rates were 63% for those treated before and 82% for those treated after October 2006 (log-rank P=0.02). Univariate Cox analysis demonstrated better overall survival among patients treated after October 2006 than among those treated beforehand (hazard ratio [HR] 0.5; 95% confidence interval [CI], 0.34-0.94); a trend toward improved survival was noted in the multivariate analysis (HR=0.47; 95% CI, 0.19-1.16; P=0.10). Significant factors in the multivariate model included HER2-directed therapy (HR=0.38; 95% CI, 0.17-0.84; P=0.02) and estrogen receptor positivity (HR=0.32; 95% CI, 0.14-0.74; P=0.01).. Survival improved in the context of the IBC clinic and prompt initiation of neoadjuvant HER2-directed therapeutics.

Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Follow-Up Studies; Humans; Inflammatory Breast Neoplasms; Mastectomy; Middle Aged; Molecular Targeted Therapy; Neoadjuvant Therapy; Radiotherapy, Adjuvant; Receptor, ErbB-2; Receptors, Estrogen; Retrospective Studies; Survival Rate; Taxoids; Time Factors; Young Adult

FOXA1 expression is a good prognostic marker for endocrine therapy in hormone-positive breast cancer. We retrospectively examined breast cancer patients with luminal human epidermal growth factor receptor 2 (HER2)-negative tumours, as defined by immunohistochemistry, who received neo-adjuvant chemotherapy (NAC) and investigated the relationship between treatment effects and FOXA1 expression.. Biopsy specimens from 103 luminal HER2-negative tumours were immunohistochemically examined. FOXA1 effects on chemo-sensitivity were also investigated employing in vitro experiments.. FOXA1 and Ki67 expressions independently predicted a pathological complete response (pCR). Knockdown of FOXA1 by siRNA boosted the chemo-effect in oestrogen receptor-positive cells. The Cox hazards model revealed a pCR to be the strongest factor predicting a good patient outcome.. Our present study showed low FOXA1 expression to be associated with a good response to NAC in luminal HER2-negative breast cancer. Improved outcomes of these patients suggest that NAC should be recommended to patients with low FOXA1 tumours.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Cell Line, Tumor; Chemotherapy, Adjuvant; Cyclophosphamide; Disease-Free Survival; Docetaxel; Epirubicin; Female; Fluorouracil; Gene Expression; Gene Knockdown Techniques; Hepatocyte Nuclear Factor 3-alpha; Humans; Kaplan-Meier Estimate; Ki-67 Antigen; Middle Aged; Neoadjuvant Therapy; Proportional Hazards Models; Receptor, ErbB-2; Receptors, Progesterone; Retrospective Studies; Taxoids; Treatment Outcome; 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

Metaplastic breast carcinoma (MBC) differs from classic invasive ductal carcinomas regarding incidence, pathogenesis, and prognosis. The purpose of this study was to compare patients with MBC with clinicopathologic and treatment-matched patients with triple-negative breast carcinoma (TNBC) in terms of response to treatment, progression, and survival.Fifty-four patients with MBC and 51 with TNBC, who were treated at Istanbul University, Institute of Oncology, between 1993 and 2014, were included in the study. After correctly matching the patients with 1 of the 2 groups, they were compared to determine differences in response to treatment, disease progression, clinical course, and survival.At a median follow-up of 28 months, 18 patients (17.1%) died and 27 (25.5%) had disease progression. Metaplastic histology was significantly correlated with worse 3-year progression-free survival (PFS) (51 ± 9% vs. 82 ± 6%, P = 0.013) and overall survival (OS) (68 ± 8% vs. 94 ± 4%, P = 0.009) compared with TNBC histology. Patients who received taxane-based chemotherapy (CT) regimens or adjuvant radiotherapy had significantly better PFS (P = 0.002 and P < 0.001) and OS (P < 0.001 and P < 0.001) compared with others. In the multivariate analysis, MBC (hazard ratio [HR]: 0.09, P < 0.001), presence of neoadjuvant chemotherapy (NACT) (HR: 12.8, P = 0.05), and metastasis development at any time during the clinical course (HR: 38.7, P < 0.001) were significant factors that decreased PFS, whereas metastasis development was the only independent prognostic factor of OS (HR: 23.8, P = 0.009).MBC is significantly correlated with worse PFS and OS compared with TNBC. Patients with MBC are resistant to conventional CT agents, and more efficient treatment regimens are required.

Topics: Adult; Antineoplastic Agents; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Disease-Free Survival; Female; Humans; Incidence; Mastectomy; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Retrospective Studies; Taxoids; Triple Negative Breast Neoplasms; Turkey

To investigate the value of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET/CT) to predict a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer.. Fifty-seven consecutive women with HER2-positive breast cancer, treated with trastuzumab plus taxane-based NAC, were prospectively included. Maximum Standardized Uptake Value of the primary tumor and axillary nodes were measured at baseline (PET₁.SUVmax) and after the first course of NAC (PET₂.SUVmax). Tumor metabolic volumes were assessed to determine Total Lesion Glycolysis (TLG). The tumor metabolic response (ΔSUVmax and ΔTLG) was calculated.. In univariate analysis, negative hormonal receptor status (p = 0.04), high tumor grade (p = 0.03), and low tumor PET₂.SUVmax (p = 0.001) were predictive of pCR. Tumor ΔSUVmax correlated with pCR (p = 0.03), provided that tumors with low metabolic activity at baseline were excluded. ΔTLG did not correlate with pCR. In multivariate analysis, tumor PET₂.SUVmax < 2.1 was the best independent predictive factor (Odds ratio =14.3; p = 0.004) with both negative and positive predictive values of 76 %. Although the metabolic features of the primary tumor did not depend on hormonal receptor status, both the baseline metabolism and early response of axillary nodes were higher if estrogen receptors were not expressed (p = 0.01 and p = 0.03, respectively).. In HER2-positive breast cancer, very low tumor residual metabolism after the first cycle of NAC (SUVmax < 2.1) was the main predictor of pCR. These results should be further explored in multicenter studies and incorporated into the design of clinical trials.

Topics: Adult; Antibodies, Monoclonal, Humanized; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Female; Fluorodeoxyglucose F18; Genes, erbB-2; Humans; Middle Aged; Multimodal Imaging; Neoadjuvant Therapy; Positron-Emission Tomography; Predictive Value of Tests; Radiopharmaceuticals; Taxoids; Tomography, X-Ray Computed; Trastuzumab; Treatment Outcome

A 32-year-old woman was seen in our hospital for complaints of bulge and pain in the sternum, and upon examination showed a lump in the left breast and enlarged left axillary lymph nodes. The patient was diagnosed with invasive ductal carcinoma with metastasis to the sternum that was T2N1M1(OSS), Stage IV, hormone-receptor-positive, and HER2-negative. Four courses each of EC and taxane therapy were performed as primary systemic chemotherapy in combination with zoledronic acid, which resulted in calcification of the osteolytic lesion in the sternum and reduced tumor mass in the breast. The patient was judged to have a partial response(PR)to the treatment. Eight months later, breast-conserving surgery and axillary lymph node dissection were performed, followed by radiation therapy to the left breast and sternum. Treatment with zoledronicac id is ongoing and postoperative hormonal therapy has been started. Four years and 4 months after the initial diagnosis, the lesion in the sternum has calcified and hardened and the patient has not had a recurrence in the same breast or elsewhere in the body.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Chemoradiotherapy; Cyclophosphamide; Epirubicin; Female; Humans; Mastectomy, Segmental; Neoplasm Staging; Sternum; Taxoids

Expression of class ΙΙΙ β-tubulin (βΙΙΙ-tubulin) correlates with tumor progression and resistance to taxane-based therapies for several human malignancies including breast cancer. However its predictive value in a neoadjuvant setting in breast cancer remains unexplored. The objective of this explorative study was to determine whether βΙΙΙ-tubulin expression in breast cancer correlated with pathologic characteristics and whether its expression was predictive of response to neoadjuvant chemotherapy.. We determined βΙΙΙ-tubulin expression in 85 breast cancers, including 41 localized breast cancers treated with primary surgery and 44 treated with neoadjuvant chemotherapy before surgery. βΙΙΙ-tubulin expression was evaluated by immunohistochemical methods and was correlated with pathologic characteristics and response to neoadjuvant chemotherapy using residual cancer burden (RCB) score.. High βΙΙΙ-tubulin expression was significantly associated with poorly differentiated high-grade breast cancers (P = .003) but not with tumor size, estrogen receptor (ER) status, or human epidermal growth factor receptor 2 (HER2)/neu overexpression. In ER(-) tumors treated with neoadjuvant chemotherapy, high βΙΙΙ-tubulin expression was associated with a significantly greater likelihood of achieving a good pathologic response to chemotherapy as reflected by lower RCB scores (P = .021).. This study reveals differential βΙΙΙ-tubulin expression in breast cancers of different histologic grades, hormone receptors, and HER2/neu status. It also suggests a potential role for βΙΙΙ-tubulin as a predictive biomarker for response in neoadjuvant chemotherapy for ER(-) breast cancer, which has not been previously reported. These data provide a strong rationale for considering βΙΙΙ-tubulin status and further validation of this marker in a large study.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Cyclophosphamide; Doxorubicin; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Middle Aged; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm Staging; Prognosis; Receptor, ErbB-2; Receptors, Estrogen; Retrospective Studies; Taxoids; Tubulin

A suggestive case of metastatic disease from breast cancer is reported. The HER-2-positive tumor was refractory to several agents, including anti-HER-2 therapy, trastuzumab, and lapatinib. After re-induction of trastuzumab in combination with activated natural killer (NK) cell injection therapy, tumor markers decreased, and finally a synergistic effect of taxane and capecitabine led to treatment response. This case suggests that multidisciplinary therapy including an immunological approach might be a breakthrough in the treatment of refractory disease.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Capecitabine; Carcinoma, Ductal, Breast; Combined Modality Therapy; Deoxycytidine; Drug Resistance, Neoplasm; Female; Fluorouracil; Humans; Killer Cells, Natural; Lapatinib; Lung Neoplasms; Middle Aged; Prognosis; Quinazolines; Receptor, ErbB-2; Salvage Therapy; Taxoids; Trastuzumab

This study aimed to determine the changes in the expression of genes for selected specific transcriptional factors that have both activating and repressing functions in in vitro ductal breast cancer cells, under the influence of paclitaxel, applying the microarray technique. The cells are treated with 60 ng/ml and 300 ng/ml doses of paclitaxel that correspond to those applied in breast cancer therapy. About 60 ng/ml doses of paclitaxel cause a statistically significant increase in expression of all the 16 analysed genes coding transcriptional factors, ranging from 1.84-fold (for PO4F2) to 4.65-fold (for LMO4) (p < 0.05) in comparison with the control cells, and enhanced the taxane mechanism of action. The 300 ng/ml doses of paclitaxel cause a cytotoxic effect in the cells. In this article, we argue that these changes in gene expression values may constitute prognostic and predictive factors in ductal breast cancer therapy.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Biomarkers, Pharmacological; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Dose-Response Relationship, Drug; Drug Synergism; Female; Gene Expression Regulation, Neoplastic; Humans; Oligonucleotide Array Sequence Analysis; Paclitaxel; Primary Cell Culture; Prognosis; Taxoids; Transcription Factors; Tumor Cells, Cultured

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

Topics: Aged; Anthracyclines; Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Chemotherapy, Adjuvant; Female; Humans; Lymphopenia; Taxoids; Treatment Outcome

We experienced a case of recurrent breast cancer resistant to prior medications, which was treated with oral S-1, a fluoropyrimidine-class anticancer drug, and exhibited the marked shrinkage of liver metastasis. The prior treatments including anthracycline and taxane were judged not effective because of the progressive disease. Then the oral treatment with S-1 was started at 120 mg/day bid. targeting metastatic lesions of the liver. At the end of the second cycle,a significant improvement was noted with a decrease rate of 82.5%. The S-1 monotherapy was thus considered to be an effective treatment for advanced or recurrent breast cancer resistant to anthracyclines and taxanes.

Topics: Anthracyclines; Antimetabolites, Antineoplastic; Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Liver Neoplasms; Mastectomy, Segmental; Middle Aged; Oxonic Acid; Pyridines; Taxoids; Tegafur

We had 2 patients with marked shrinkage of liver metastasis by administration of the oral fluorinated pyrimidine anticancer drug S-1 for advanced/recurrent breast cancer that was resistant to taxane and another antitumor drugs. Both patients almost completed the full dose through the whole course of treatment,and the drug showed good tolerability. S-1 was considered to possess beneficial antitumor efficacy and tolerability and to be promising as home chemotherapy for advanced/recurrent breast cancer.

Topics: Administration, Oral; Anthracyclines; Antimetabolites, Antineoplastic; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Liver Neoplasms; Middle Aged; Oxonic Acid; Pyridines; Taxoids; Tegafur

We had 3 patients with recurrent/advanced breast cancer in whom a notable reduction in the size of the targeted tumors was seen following administration of S-1 (TS-1), a new oral pyrimidine fluoride anticancer drug. All of the patients had received taxane and/or anthracycline anticancer drugs as prior therapy; however, they were judged to be non-responsive to the drugs. The size of the targeted tumor decreased to 55.7% after 3 courses of the therapy in Patient 1. The tumor disappeared at completion of the third course in Patient 2, although the therapy was temporarily suspended during the second course due to adverse drug reactions, and the therapy was then resumed after 2-week drug withdrawal. Patient 3 was able to undergo long-term therapy, consisting of 8 courses for 11 months, and the size of the tumor reduced to 58.1%. No serious adverse drug reactions to S-1 occurred in our 3 patients. It is thought that less toxicity enabled Patient 3 to undergo long-term therapy. We consider S-1 to be a useful anticancer drug for treatment of taxane and/or anthracycline resistant recurrent breast cancer.

Topics: Aged; Anthracyclines; Antimetabolites, Antineoplastic; Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Chemotherapy, Adjuvant; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Lymph Node Excision; Lymph Nodes; Mastectomy, Segmental; Middle Aged; Oxonic Acid; Pyridines; Taxoids; Tegafur

A patient with lung metastasis of breast cancer was reported. The patient underwent surgery in December, 1999. Her breast cancer then recurred in December, 2000. After treatment failure with anthracycline and taxane antitumor drugs,she participated in a phase II study of S-1, a fluorinated pyrimidine anticancer drug, which was given orally at 80 mg/m2/day (2 doses). After completion of 4 courses of treatment,the target lesions of the lung metastasis markedly shrunk by 47.5% as compared with the pretreatment. Because salvage therapy with S-1 alone showed good antitumor efficacy and beneficial tolerability when the standard dosage was maintained, it was considered that this home therapy was effective for advanced/recurrent breast cancer that was resistant to anthracycline and taxane antitumor drugs.

Topics: Administration, Oral; Anthracyclines; Antimetabolites, Antineoplastic; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Clinical Trials, Phase II as Topic; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Middle Aged; Oxonic Acid; Pyridines; Quality of Life; Salvage Therapy; Taxoids; Tegafur