taxane and Carcinoma--Intraductal--Noninfiltrating

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

To quantify the prevalence of neurological complications among breast cancer patients at one and three years after diagnosis, and to identify factors associated with neuropathic pain (NP) and chemotherapy-induced peripheral neuropathy (CIPN).. Prospective cohort study including 475 patients with newly diagnosed breast cancer, recruited among those proposed for surgical treatment (Portuguese Institute of Oncology, Porto). Patients underwent a neurological evaluation and had their cognitive function assesses with the Montreal Cognitive Assessment, before treatment and at one and three years after enrollment. We estimated the prevalence of each neurological complication, and odds ratios (OR), adjusted for socio-demographic and clinical characteristics, to identify factors associated with NP and CIPN.. More than half of the patients [54.7%, 95% confidence interval (95%CI): 50.2-59.2] presented at least one neurological complication, at one or at three years after cancer diagnosis. Between the first and the third year of follow-up, there was an increase in the prevalence of NP (from 21.1% to 23.6%), cognitive impairment (from 7.2% to 8.2%), cerebrovascular disease (from 0.6% to 1.5%) and brain metastasis (from 0.0% to 0.6%). The prevalence of CIPN decreased from 14.1% to 12.6%. Axillary lymph node dissection was associated with NP at one year (OR = 2.75, 95%CI: 1.34-5.63) and chemotherapy with NP at three years (OR = 2.10, 95%CI: 1.20-3.67). Taxane-based chemotherapy was strongly associated with prevalence of CIPN at one and three years.. Neurological complications are frequent even three years after cancer diagnosis and NP remained the major contributor to the burden of these conditions among survivors.

Topics: Adult; Antineoplastic Agents; Axilla; Brain Neoplasms; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Intraductal, Noninfiltrating; Cerebrovascular Disorders; Cognitive Dysfunction; Female; Follow-Up Studies; Humans; Lymph Node Excision; Middle Aged; Neuralgia; Neurotoxicity Syndromes; Peripheral Nervous System Diseases; Prevalence; Prospective Studies; Risk Factors; Survivors; Taxoids