Vicente Valero - Academia.edu (original) (raw)

Papers by Vicente Valero

Journal of Clinical Oncology, 2013

1005 Background: By gene profiling, Lehmann et al. (J Clin Invest 121:2750-2767, 2011) reported t... more 1005 Background: By gene profiling, Lehmann et al. (J Clin Invest 121:2750-2767, 2011) reported that triple-negative breast cancer (TNBC) can be classified into 6 clusters—basal-like 1 (BL1), basal-like 2 (BL2), immunomodulatory (IM), mesenchymal (M), mesenchymal stem-like (MSL), and luminal androgen receptor (LAR)—plus an unstable (UNS) cluster. While it is clear that patients with TNBC differently respond to chemotherapy, the clinical relevance of these molecular TNBC subtypes is unknown. Methods: We qualitatively reproduced the Lehmann et al. experiments using Affymetrix CEL files from the public datasets. We identified 130 TNBC gene expression microarrays obtained from 03/00 to 03/10. All patients had received neoadjuvant chemotherapy containing sequential taxane and anthracycline-based regimens and had evaluable pathological tumor response data. Median follow-up was 68.1 months. (5.1-147.5). We classified TNBC samples using Lehmann’s gene signatures, then performed Fisher's...

Oncology Reviews, 2017

Triple negative breast (TNBC) cancer constitutes a heterogeneous group of disease with histologic... more Triple negative breast (TNBC) cancer constitutes a heterogeneous group of disease with histologic and molecular differences. Complete pathologic response to neoadjuvant chemotherapy (NACT) in TNBC is associated with improved outcomes. Efforts have been made in identifying drug combinations that will increase the response rate to preoperative chemotherapy. In this review we present recent studies that have incorporated carboplatin (Cb) in the NACT of TNBC. We discuss the homologous recombination deficiency score and the somatic or germline mutation for BRCA as potential biomarkers for future selection of patients that could benefit from the addition of Cb to NACT.

The Oncologist, 2011

Background. Numerous studies have demonstrated that expression of estrogen/progesterone receptor ... more Background. Numerous studies have demonstrated that expression of estrogen/progesterone receptor (ER/PR) and human epidermal growth factor receptor (HER)-2 is important for predicting overall survival (OS), distant relapse (DR), and locoregional relapse (LRR) in early and advanced breast cancer patients. However, these findings have not been confirmed for inflammatory breast cancer (IBC), which has different biological features than non-IBC. Methods. We retrospectively analyzed the records of 316 women who presented to MD Anderson Cancer Center in 1989–2008 with newly diagnosed IBC without distant metastases. Most patients received neoadjuvant chemotherapy, mastectomy, and postmastectomy radiation. Patients were grouped according to receptor status: ER+ (ER+/PR+ and HER-2−; n = 105), ER+HER-2+ (ER+/PR+ and HER-2+; n = 37), HER-2+ (ER−/PR− and HER-2+; n = 83), or triple-negative (TN) (ER−PR−HER-2−; n = 91). Kaplan–Meier and Cox proportional hazards methods were used to assess LRR, DR...

Journal of Clinical Oncology, 2011

Purpose Docetaxel-trastuzumab (TH) is effective therapy for HER2-amplified metastatic breast canc... more Purpose Docetaxel-trastuzumab (TH) is effective therapy for HER2-amplified metastatic breast cancer (MBC). Preclinical findings of synergy between docetaxel, carboplatin, and trastuzumab (TCH) prompted a phase III randomized trial comparing TCH with TH in patients with HER2-amplified MBC. Patients and Methods Two hundred sixty-three patients were randomly assigned to receive eight 3-week cycles of TH (trastuzumab plus docetaxel 100 mg/m2) or TCH (trastuzumab plus carboplatin at area under the serum concentration-time curve 6 and docetaxel 75 mg/m2). Trastuzumab was given at 4 mg/kg loading dose followed by a 2 mg/kg dose once per week during chemotherapy, and then 6 mg/kg once every 3 weeks until progression. Results Patient characteristics were balanced between groups. There was no significant difference between TH and TCH in terms of the primary end point, time to progression (medians of 11.1 and 10.4 months, respectively; hazard ratio, 0.914; 95% CI, 0.694 to 1.203; P = .57), res...

Cancer, 1999

Vinorelbine given by weekly bolus injection is active and less toxic than bolus vinblastine in th... more Vinorelbine given by weekly bolus injection is active and less toxic than bolus vinblastine in the treatment of patients with metastatic breast carcinoma. Vinblastine given by 5-day continuous infusion showed a steep dose-response curve. Pharmacokinetic studies of vinorelbine showed that it is possible to achieve a comparable antitumor effect with a smaller amount of the drug if it is given by continuous infusion. The purpose of this study was to determine the efficacy of vinorelbine given by 96-hour continuous infusion to patients with refractory metastatic breast carcinoma patients. Between May 1996 and August 1997, 47 patients with metastatic breast carcinoma were registered into the study. All patients previously had received doxorubicin and 70% had undergone prior paclitaxel treatment. Approximately 56% of the patients had >/=2 metastatic sites. All patients received vinorelbine according to the following dose schedule: 8 mg bolus followed by 11 mg/m(2) by continuous infusion over 24 hours every 4 days every 3 weeks. Forty-four patients were evaluable for response. A total of 193 cycles were administered. The overall response rate was 16% (2 patients achieved a complete response and 5 patients achieved a partial response). The median duration of response was 4.3 months and the median overall survival was 8.6 months. Patients with visceral metastases and/or multiple sites of involvement had shorter durations of response than patients with only soft tissue disease or single-site metastasis (3.1 months vs. 4. 9 months) and shorter overall survival (8.1 months vs. 12 months). Dose reductions were necessary due to cumulative stomatitis and/or fatigue in 12 cycles and neutropenia and/or infection in 13 cycles. Due to toxicity, a revised maximum tolerated dose for continuous infusion vinorelbine is proposed by the authors: 8 mg intravenously over 10 minutes followed by 10 mg/m(2) by continuous infusion over 24 hours every 4 days. The current dose schedule did not offer an advantage either in response rates or survival over the weekly vinorelbine bolus injection in doxorubicin-resistant and paclitaxel-resistant patients.

Breast Diseases: A Year Book Quarterly, 2007

We developed a multigene predictor of pathologic complete response (pCR) to preoperative weekly p... more We developed a multigene predictor of pathologic complete response (pCR) to preoperative weekly paclitaxel and fluorouracil-doxorubicin-cyclophosphamide (T/FAC) chemotherapy and assessed its predictive accuracy on independent cases. Patients and Methods One hundred thirty-three patients with stage I-III breast cancer were included. Pretreatment gene expression profiling was performed with oligonecleotide microarrays on fine-needle aspiration specimens. We developed predictors of pCR from 82 cases and assessed accuracy on 51 independent cases. Results Overall pCR rate was 26% in both cohorts. In the training set, 56 probes were identified as differentially expressed between pCR versus residual disease, at a false discovery rate of 1%. We examined the performance of 780 distinct classifiers (set of genes ϩ prediction algorithm) in full cross-validation. Many predictors performed equally well. A nominally best 30-probe set Diagonal Linear Discriminant Analysis classifier was selected for independent validation. It showed significantly higher sensitivity (92% v 61%) than a clinical predictor including age, grade, and estrogen receptor status. The negative predictive value (96% v 86%) and area under the curve (0.877 v 0.811) were nominally better but not statistically significant. The combination of genomic and clinical information yielded a predictor not significantly different from the genomic predictor alone. In 31 samples, RNA was hybridized in replicate with resulting predictions that were 97% concordant. Conclusion A 30-probe set pharmacogenomic predictor predicted pCR to T/FAC chemotherapy with high sensitivity and negative predictive value. This test correctly identified all but one of the patients who achieved pCR (12 of 13 patients) and all but one of those who were predicted to have residual disease had residual cancer (27 of 28 patients).

Journal of Clinical Oncology, 2015

Several indices have been developed to predict overall survival (OS) in patients with breast canc... more Several indices have been developed to predict overall survival (OS) in patients with breast cancer with brain metastases, including the breast graded prognostic assessment (breast-GPA), comprising age, tumor subtype, and Karnofsky performance score. However, number of brain metastases-a highly relevant clinical variable-is less often incorporated into the final model. We sought to validate the existing breast-GPA in an independent larger cohort and refine it integrating number of brain metastases. Data were retrospectively gathered from a prospectively maintained institutional database. Patients with newly diagnosed brain metastases from 1996 to 2013 were identified. After validating the breast-GPA, multivariable Cox regression and recursive partitioning analysis led to the development of the modified breast-GPA. The performances of the breast-GPA and modified breast-GPA were compared using the concordance index. In our cohort of 1,552 patients, the breast-GPA was validated as a prognostic tool for OS (P < .001). In multivariable analysis of the breast-GPA and number of brain metastases (> three v ≤ three), both were independent predictors of OS. We therefore developed the modified breast-GPA integrating a fourth clinical parameter. Recursive partitioning analysis reinforced the prognostic significance of these four factors. Concordance indices were 0.78 (95% CI, 0.77 to 0.80) and 0.84 (95% CI, 0.83 to 0.85) for the breast-GPA and modified breast-GPA, respectively (P < .001). The modified breast-GPA incorporates four simple clinical parameters of high prognostic significance. This index has an immediate role in the clinic as a formative part of the clinician's discussion of prognosis and direction of care and as a potential patient selection tool for clinical trials.

Oncotarget, Jan 30, 2014

Accumulating evidence highlights the potential role of long non-coding RNAs (lncRNAs) as biomarke... more Accumulating evidence highlights the potential role of long non-coding RNAs (lncRNAs) as biomarkers and therapeutic targets in solid tumors. However, the role of lncRNA expression in human breast cancer biology, prognosis and molecular classification remains unknown. Herein, we established the lncRNA profile of 658 infiltrating ductal carcinomas of the breast from The Cancer Genome Atlas project. We found lncRNA expression to correlate with the gene expression and chromatin landscape of human mammary epithelial cells (non-transformed) and the breast cancer cell line MCF-7. Unsupervised consensus clustering of lncRNA revealed four subgroups that displayed different prognoses. Gene set enrichment analysis for cis- and trans-acting lncRNAs showed enrichment for breast cancer signatures driven by master regulators of breast carcinogenesis. Interestingly, the lncRNA HOTAIR was significantly overexpressed in the HER2-enriched subgroup, while the lncRNA HOTAIRM1 was significantly overexpre...

Clinical Breast Cancer, 2010

Sentinel lymph node (SLN) dissection (SLND) has largely replaced axillary lymph node dissection (... more Sentinel lymph node (SLN) dissection (SLND) has largely replaced axillary lymph node dissection (ALND) as the standard of care for lymph node staging in patients with clinically node-negative breast cancer. Multiple studies have shown that SLN status accurately predicts the status of the remaining nodes in the axillary basin, enabling the surgeon to select patients who are more likely to benefit from ALND. 1-3 This minimally invasive procedure offers an effective means of axillary staging, while significantly reducing the surgical morbidities associated with ALND and improving the overall quality of life postoperatively. Several investigators have reported that SLN identification rates are lower in older breast cancer patients. 2,6,7 In a single-institution prospective trial, Sener and colleagues reported age as a predictive factor for failure to identify SLNs in node-negative patients 70 years of age and older. 7 In addition, the National Surgical Adjuvant Breast and Bowel Project B-32 and the American College of Surgeons Oncology Group Z0010 trials reported similar results. 2,6 The reasons for lower SLN identification rates in older patients in these studies were not clearly defined. In the current study, we reviewed the technical outcomes of SLND in a large cohort of patients with breast cancer at a single institution and evaluated clinicopathologic factors that might have influenced the success of the procedure. In addition, we compared SLN identification rates in breast cancer patients 70 years and older versus patients younger than 70 years of age.

Journal of Cancer, 2014

Many phase II trials investigated the combination of Gemcitabine (G) and Vinorelbine (V) in the t... more Many phase II trials investigated the combination of Gemcitabine (G) and Vinorelbine (V) in the treatment of metastatic breast cancer (MBC) with variable outcomes. This study was conducted to explore whether this combination was effective and tolerable in MBC patients who were heavily pretreated with anthracyclines and taxanes. A phase I study was conducted first to establish the maximum tolerated dose (MTD) of the G and V combination in MBC patients. Then, a phase II study evaluated the response rates, the median time to progression (TTP), the overall survival (OS) as well as the toxicities resulting from this combination at the MTD. Nine patients were enrolled in the phase I study. The MTD was identified as 700mg/m(2) of G on days 1 and 8 in combination with 15 mg/m(2) of V on days 2 and 9, every 21 days. Twenty-one of 25 patients involved in the phase II study were evaluable for response. No complete or partial responses were achieved; 6 patients (24.0%) had stable disease and 15...

Clinical breast cancer, 2012

This retrospective analysis aimed to determine whether early dose reduction impacts the efficacy ... more This retrospective analysis aimed to determine whether early dose reduction impacts the efficacy of ixabepilone plus capecitabine in women with metastatic breast cancer (MBC). In 2 phase III trials, patients (N = 1973) with anthracycline/taxane-pretreated MBC were randomized to receive ixabepilone 40 mg/m(2) on day 1 plus capecitabine 1000 mg/m(2) twice daily (BID) on days 1 to 14 or single-agent capecitabine 1250 mg/m(2) BID on days 1 to 14 of a 3-week course. Because of the similar design and populations, data from trials were pooled to evaluate efficacy of the combination regimen among women who did or did not undergo ixabepilone dose reduction during the first 4 courses. To adjust for bias resulting from selecting patients with inherently better outcome based on longer treatment durations, these analyses were restricted to patients who received ≥ 4 courses of ixabepilone. The pooled cohort included 566 patients with measurable disease who were evaluable for efficacy. Patients wh...

Molecular cancer therapeutics, 2014

Patients with metastatic triple-negative breast cancer (TNBC) have poor treatment outcomes. We re... more Patients with metastatic triple-negative breast cancer (TNBC) have poor treatment outcomes. We reviewed the electronic records of consecutive patients with metastatic TNBC treated in phase I clinic at MD Anderson Cancer Center (Houston, TX) between Augu st 2005 and May 2012. One hundred and six patients received at least 1 phase I trial. Twelve of 98 evaluable patients (12%) had either complete response (CR; n = 1), partial response (PR; n = 7), or stable disease ≥ 6 months (SD; n = 4). Patients treated on matched therapy (n = 16) compared with those on nonmatched therapy (n = 90) had improved SD ≥ 6 months/PR/CR (33% vs. 8%; P = 0.018) and longer progression-free survival (PFS; median, 6.4 vs. 1.9 months; P = 0.001). Eleven of 57 evaluable patients (19%) treated with combination chemotherapy and targeted therapy had SD ≥ 6 months/PR/CR versus 1 of 41 evaluable patients (2%) treated on other phase I trials (P = 0.013), and longer PFS (3.0 vs. 1.6 months; P < 0.0001). Patients wit...

Surgery, 2012

BACKGROUND-The oncologic benefit of resecting liver metastases in breast cancer patients is uncle... more BACKGROUND-The oncologic benefit of resecting liver metastases in breast cancer patients is unclear. This study was performed to identify predictors of survival after hepatectomy. [1997][1998][1999][2000][2001][2002][2003][2004][2005][2006][2007][2008][2009][2010] 86 patients underwent resection of breast cancer liver metastases (BCLM). Clinicopathologic characteristics of the primary tumor, timing of metastasis development and treatment were recorded. Response to pre-hepatectomy chemotherapy was evaluated according to RECIST criteria, and the best response to chemotherapy during treatment and the response immediately before hepatectomy were noted. Univariate and multivariate analyses were performed to identify predictors of disease-free (DFS) and overall survival (OS).

Plastic and Reconstructive Surgery, 2011

The authors examined the safety of a protocol for planned skin-preserving delayed breast reconstr... more The authors examined the safety of a protocol for planned skin-preserving delayed breast reconstruction after postmastectomy radiotherapy with placement of a tissue expander for patients with locally advanced breast cancer (stages IIB and III). The authors compared 47 patients treated according to the protocol between December 2003 and May 2008 with 47 disease-stage-matched control patients who underwent standard delayed reconstruction after postmastectomy radiotherapy (no skin preservation or tissue expander) during the same period. Protocol-group complication rates were 21 percent for skin-preserving mastectomy and placement of the expander (stage 1), 5 percent for postmastectomy radiotherapy, 25 percent for expander reinflation after radiotherapy, and 24 percent for skin-preserving delayed reconstruction. The complication rate for standard delayed reconstruction was 38 percent. Tissue-expander loss rates were 32 percent overall, 9 percent for stage 1, 5 percent for postmastectomy radiotherapy, and 22 percent for reinflation. Wound-healing complications after reconstruction occurred in 3 percent of protocol-group and 10 percent of control-group patients. The median follow-up time for patients still alive at last follow-up was 40 months (range, 8.5 to 85.3 months). Three-year recurrence-free survival rates were 92 percent (95 percent CI, 83 to 100 percent) and 86 percent (95 percent CI, 76 to 98 percent) for the protocol and control groups, respectively (p = 0.87). In patients with locally advanced breast cancer, skin-preserving mastectomy with a deflated tissue expander on the chest wall during postmastectomy radiotherapy does not increase locoregional recurrence risk and is associated with lower complication rates of definitive reconstruction.

Oncology, 2009

A phase I study was initiated to determine the maximum tolerated dose (MTD) of prolonged-infusion... more A phase I study was initiated to determine the maximum tolerated dose (MTD) of prolonged-infusion gemcitabine combined with cyclophosphamide in patients with metastatic breast carcinoma (MBC). Patients with MBC were treated with gemcitabine infusion at 10 mg/m2/min and cyclophosphamide by intravenous piggyback injection, 4 h after initiation of the infusion. We treated 3-6 patients at a particular dose level until the MTD was determined. Overall, 44 patients received a total of 197 courses of therapy. Both drugs were given on days 1, 8 and 15 to 14 patients (68 courses). Delayed white blood cell recovery necessitated first protocol amendment to drop cyclophosphamide on days 8 and 15 in 9 patients (43 cycles). A second amendment was needed to drop gemcitabine on day 15 because of thrombocytopenia in 21 patients (86 courses). The dose-limiting toxicity was thrombocytopenia. The MTD of an optimal dose schedule was 800 mg/m2 gemcitabine infused at a rate of 10 mg/m2/min on days 1 and 8, and 400 mg/m2 cyclophosphamide, by intravenous piggyback injection, on day 1, 4 h after initiation of the gemcitabine infusion. The MTD can be given safely every 4 weeks to patients with MBC. Phase II studies are warranted to evaluate the clinical activity of this therapy.

Clinical Breast Cancer, 2015

Recurrence score (RS) derived from a 21-gene reverse transcriptase-polymerase chain reaction assa... more Recurrence score (RS) derived from a 21-gene reverse transcriptase-polymerase chain reaction assay is used to stratify patients with early-stage estrogen receptor-positive, HER2-normal breast cancer into 3 groups on the basis of 10-year distant metastasis risk: low, intermediate, and high. Published data are limited regarding the effect of RS on choice of adjuvant therapy for T1 breast cancer. We investigated the relationship between RS and choice of adjuvant therapy, prognosis, and benefit of chemotherapy (CT) in stage I breast cancer. We reviewed the records of 1030 patients with estrogen receptor-positive, HER2-normal stage I breast cancer and RS available. RSs were correlated with clinicopathologic characteristics, treatment, and outcome. Patients with pathologic (p)T1a, pT1b, and pT1c disease did not differ in distribution of low, intermediate, and high RS (P = .673). Overall, fewer than 10% of patients had a high RS. Histologic grade 1, nuclear grade 1, and low Ki-67 expression had only 1%, 0%, and 6% of high RSs, respectively. Among patients with intermediate RSs, 41% with pT1b and 46% with pT1c disease received CT. Among patients with intermediate RSs, for pT1b disease, distant disease-free survival (DDFS) did not differ between hormonal therapy (HT) alone and CT with HT (P = .752); for pT1c, DDFS was superior for CT with HT (P = .020). Histologic grade was the only independent prognostic factor of DDFS (P = .0007, 1 vs. 3; P = .035, 2 vs. 3); RS did not predict DDFS (P = .083, high vs. low; P = .066, intermediate vs. low). The added value of RS to known prognostic factors appears limited to patients with pT1b breast cancer. However, this study lacked long-term follow-up.

The Lancet, 2000

Docetaxel and vinorelbine as combined treatment for metastatic breast cancer can have the dose-li... more Docetaxel and vinorelbine as combined treatment for metastatic breast cancer can have the dose-limiting toxic effects of mucositis and neutropenic fever. We report unexpected ischaemic colitis in six patients associated with docetaxel-based therapy, three of whom were treated in a phase I study designed to establish the maximum tolerated dose of this combination with the prophylactic use of granulocyte-colony-stimulating factor. Between August, 1997, and December, 1998, 14 patients with metastatic breast cancer were treated with vinorelbine, docetaxel, and granulocyte-colony-stimulating factor in a phase I study. Three patients developed colitis similar to that seen in typhlitis. Three additional patients were identified during scheduled review of toxic effects in patients participating in clinical trials involving docetaxel. Three patients on combined vinorelbine and docetaxel developed colitis-like symptoms. Two patients died, one from necrotic bowel and the other from neutropenic fever and colitis. Two of the patients presented on day 7 and day 8 of chemotherapy, respectively, with neutropenic fever and abdominal pain; the third patient developed neutropenia without fever and abdominal pain on day 8. The other three patients were treated with docetaxel, docetaxel and pamidronate disodium, or docetaxel and cyclophosphamide. All three patients presented with abdominal pain on days 10, 5, and 4, respectively. One had non-neutropenic fever, another had neutropenic fever, and the third was afebrile and non-neutropenic at the time of presentation with abdominal pain. Three patients had blood in their diarrhoea, abdominal tenderness, or both. Computed tomography of the abdomen and pelvis showed features of colitis in three patients. This serious complication may result from the use of docetaxel and may be exacerbated by its combination with vinorelbine. Study of hospital-based patients treated with taxane-based chemotherapy is underway to find out the frequency of such complications.

International Journal of Radiation Oncology*Biology*Physics, 2015

We sought to determine the rate at which regional nodal ultrasonography would increase the nodal ... more We sought to determine the rate at which regional nodal ultrasonography would increase the nodal disease stage in patients with triple-negative breast cancer (TNBC) beyond the clinical stage determined by physical examination and mammography alone, and significantly affect the treatments delivered to these patients. We retrospectively reviewed the charts of women with stages I to III TNBC who underwent physical examination, mammography, breast and regional nodal ultrasonography with needle biopsy of abnormal nodes, and definitive local-regional treatment at our institution between 2004 and 2011. The stages of these patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; disease with and without ultrasonography of the regional nodal basins were compared using the Pearson χ(2) test. Definitive treatments of patients whose nodal disease was upstaged on the basis of ultrasonographic findings were compared to those of patients whose disease stage remained the same. A total of 572 women met the study requirements. In 111 (19.4%) of these patients, regional nodal ultrasonography with needle biopsy resulted in an increase in disease stage from the original stage by physical examination and mammography alone. Significantly higher percentages of patients whose nodal disease was upstaged by ultrasonographic findings compared to that in patients whose disease was not upstaged underwent neoadjuvant systemic therapy (91.9% and 51.2%, respectively; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.0001), axillary lymph node dissection (99.1% and 34.5%, respectively; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.0001), and radiation to the regional nodal basins (88.2% and 29.1%, respectively; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.0001). Regional nodal ultrasonography in TNBC frequently changes the initial clinical stage and plays an important role in treatment planning.

Journal of Geriatric Oncology, 2013

Data on chemotherapy regimens in elderly patients with metastatic breast cancer (MBC) are limited... more Data on chemotherapy regimens in elderly patients with metastatic breast cancer (MBC) are limited. The aim of this retrospective pooled analysis was to determine efficacy and safety of ixabepilone plus capecitabine versus capecitabine alone in patients with MBC aged ≥ 65 years. A total of 1973 patients with MBC previously treated with or resistant to anthracyclines and taxanes were randomized in two open-label, multinational, phase 3 studies (study 046 and study 048). Patients received ixabepilone (40 mg/m(2) as a 3-hour intravenous infusion every 3 weeks) plus oral capecitabine (1000 mg/m(2) administered twice each day), or capecitabine alone (1250 mg/m(2) twice each day). In total, 251 randomized patients were aged ≥ 65 years (ixabepilone plus capecitabine, n=116; capecitabine monotherapy, n=135). Efficacy results were consistent in patients aged &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;65 and ≥ 65 years with respect to the observed improvement in progression-free survival and objective response rate with ixabepilone plus capecitabine compared with capecitabine alone. No significant differences in overall survival between arms were observed for either subgroup. In the ixabepilone plus capecitabine arm, grade 3/4 hematologic adverse events (AEs) were similar in both subgroups except leukopenia and febrile neutropenia, which had a higher incidence in patients aged ≥ 65 years. The majority of grade 3/4 nonhematologic AEs were similar in the two subgroups, including fatigue, peripheral sensory neuropathy, and hand-foot syndrome. The combination of ixabepilone plus capecitabine maintains its efficacy in elderly patients with anthracycline and taxane pretreated MBC, with a similar safety profile to patients aged &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 65 years.

Journal of Clinical Oncology, 2013

1005 Background: By gene profiling, Lehmann et al. (J Clin Invest 121:2750-2767, 2011) reported t... more 1005 Background: By gene profiling, Lehmann et al. (J Clin Invest 121:2750-2767, 2011) reported that triple-negative breast cancer (TNBC) can be classified into 6 clusters—basal-like 1 (BL1), basal-like 2 (BL2), immunomodulatory (IM), mesenchymal (M), mesenchymal stem-like (MSL), and luminal androgen receptor (LAR)—plus an unstable (UNS) cluster. While it is clear that patients with TNBC differently respond to chemotherapy, the clinical relevance of these molecular TNBC subtypes is unknown. Methods: We qualitatively reproduced the Lehmann et al. experiments using Affymetrix CEL files from the public datasets. We identified 130 TNBC gene expression microarrays obtained from 03/00 to 03/10. All patients had received neoadjuvant chemotherapy containing sequential taxane and anthracycline-based regimens and had evaluable pathological tumor response data. Median follow-up was 68.1 months. (5.1-147.5). We classified TNBC samples using Lehmann’s gene signatures, then performed Fisher's...

Oncology Reviews, 2017

Triple negative breast (TNBC) cancer constitutes a heterogeneous group of disease with histologic... more Triple negative breast (TNBC) cancer constitutes a heterogeneous group of disease with histologic and molecular differences. Complete pathologic response to neoadjuvant chemotherapy (NACT) in TNBC is associated with improved outcomes. Efforts have been made in identifying drug combinations that will increase the response rate to preoperative chemotherapy. In this review we present recent studies that have incorporated carboplatin (Cb) in the NACT of TNBC. We discuss the homologous recombination deficiency score and the somatic or germline mutation for BRCA as potential biomarkers for future selection of patients that could benefit from the addition of Cb to NACT.

The Oncologist, 2011

Background. Numerous studies have demonstrated that expression of estrogen/progesterone receptor ... more Background. Numerous studies have demonstrated that expression of estrogen/progesterone receptor (ER/PR) and human epidermal growth factor receptor (HER)-2 is important for predicting overall survival (OS), distant relapse (DR), and locoregional relapse (LRR) in early and advanced breast cancer patients. However, these findings have not been confirmed for inflammatory breast cancer (IBC), which has different biological features than non-IBC. Methods. We retrospectively analyzed the records of 316 women who presented to MD Anderson Cancer Center in 1989–2008 with newly diagnosed IBC without distant metastases. Most patients received neoadjuvant chemotherapy, mastectomy, and postmastectomy radiation. Patients were grouped according to receptor status: ER+ (ER+/PR+ and HER-2−; n = 105), ER+HER-2+ (ER+/PR+ and HER-2+; n = 37), HER-2+ (ER−/PR− and HER-2+; n = 83), or triple-negative (TN) (ER−PR−HER-2−; n = 91). Kaplan–Meier and Cox proportional hazards methods were used to assess LRR, DR...

Journal of Clinical Oncology, 2011

Purpose Docetaxel-trastuzumab (TH) is effective therapy for HER2-amplified metastatic breast canc... more Purpose Docetaxel-trastuzumab (TH) is effective therapy for HER2-amplified metastatic breast cancer (MBC). Preclinical findings of synergy between docetaxel, carboplatin, and trastuzumab (TCH) prompted a phase III randomized trial comparing TCH with TH in patients with HER2-amplified MBC. Patients and Methods Two hundred sixty-three patients were randomly assigned to receive eight 3-week cycles of TH (trastuzumab plus docetaxel 100 mg/m2) or TCH (trastuzumab plus carboplatin at area under the serum concentration-time curve 6 and docetaxel 75 mg/m2). Trastuzumab was given at 4 mg/kg loading dose followed by a 2 mg/kg dose once per week during chemotherapy, and then 6 mg/kg once every 3 weeks until progression. Results Patient characteristics were balanced between groups. There was no significant difference between TH and TCH in terms of the primary end point, time to progression (medians of 11.1 and 10.4 months, respectively; hazard ratio, 0.914; 95% CI, 0.694 to 1.203; P = .57), res...

Cancer, 1999

Vinorelbine given by weekly bolus injection is active and less toxic than bolus vinblastine in th... more Vinorelbine given by weekly bolus injection is active and less toxic than bolus vinblastine in the treatment of patients with metastatic breast carcinoma. Vinblastine given by 5-day continuous infusion showed a steep dose-response curve. Pharmacokinetic studies of vinorelbine showed that it is possible to achieve a comparable antitumor effect with a smaller amount of the drug if it is given by continuous infusion. The purpose of this study was to determine the efficacy of vinorelbine given by 96-hour continuous infusion to patients with refractory metastatic breast carcinoma patients. Between May 1996 and August 1997, 47 patients with metastatic breast carcinoma were registered into the study. All patients previously had received doxorubicin and 70% had undergone prior paclitaxel treatment. Approximately 56% of the patients had &gt;/=2 metastatic sites. All patients received vinorelbine according to the following dose schedule: 8 mg bolus followed by 11 mg/m(2) by continuous infusion over 24 hours every 4 days every 3 weeks. Forty-four patients were evaluable for response. A total of 193 cycles were administered. The overall response rate was 16% (2 patients achieved a complete response and 5 patients achieved a partial response). The median duration of response was 4.3 months and the median overall survival was 8.6 months. Patients with visceral metastases and/or multiple sites of involvement had shorter durations of response than patients with only soft tissue disease or single-site metastasis (3.1 months vs. 4. 9 months) and shorter overall survival (8.1 months vs. 12 months). Dose reductions were necessary due to cumulative stomatitis and/or fatigue in 12 cycles and neutropenia and/or infection in 13 cycles. Due to toxicity, a revised maximum tolerated dose for continuous infusion vinorelbine is proposed by the authors: 8 mg intravenously over 10 minutes followed by 10 mg/m(2) by continuous infusion over 24 hours every 4 days. The current dose schedule did not offer an advantage either in response rates or survival over the weekly vinorelbine bolus injection in doxorubicin-resistant and paclitaxel-resistant patients.

Breast Diseases: A Year Book Quarterly, 2007

We developed a multigene predictor of pathologic complete response (pCR) to preoperative weekly p... more We developed a multigene predictor of pathologic complete response (pCR) to preoperative weekly paclitaxel and fluorouracil-doxorubicin-cyclophosphamide (T/FAC) chemotherapy and assessed its predictive accuracy on independent cases. Patients and Methods One hundred thirty-three patients with stage I-III breast cancer were included. Pretreatment gene expression profiling was performed with oligonecleotide microarrays on fine-needle aspiration specimens. We developed predictors of pCR from 82 cases and assessed accuracy on 51 independent cases. Results Overall pCR rate was 26% in both cohorts. In the training set, 56 probes were identified as differentially expressed between pCR versus residual disease, at a false discovery rate of 1%. We examined the performance of 780 distinct classifiers (set of genes ϩ prediction algorithm) in full cross-validation. Many predictors performed equally well. A nominally best 30-probe set Diagonal Linear Discriminant Analysis classifier was selected for independent validation. It showed significantly higher sensitivity (92% v 61%) than a clinical predictor including age, grade, and estrogen receptor status. The negative predictive value (96% v 86%) and area under the curve (0.877 v 0.811) were nominally better but not statistically significant. The combination of genomic and clinical information yielded a predictor not significantly different from the genomic predictor alone. In 31 samples, RNA was hybridized in replicate with resulting predictions that were 97% concordant. Conclusion A 30-probe set pharmacogenomic predictor predicted pCR to T/FAC chemotherapy with high sensitivity and negative predictive value. This test correctly identified all but one of the patients who achieved pCR (12 of 13 patients) and all but one of those who were predicted to have residual disease had residual cancer (27 of 28 patients).

Journal of Clinical Oncology, 2015

Several indices have been developed to predict overall survival (OS) in patients with breast canc... more Several indices have been developed to predict overall survival (OS) in patients with breast cancer with brain metastases, including the breast graded prognostic assessment (breast-GPA), comprising age, tumor subtype, and Karnofsky performance score. However, number of brain metastases-a highly relevant clinical variable-is less often incorporated into the final model. We sought to validate the existing breast-GPA in an independent larger cohort and refine it integrating number of brain metastases. Data were retrospectively gathered from a prospectively maintained institutional database. Patients with newly diagnosed brain metastases from 1996 to 2013 were identified. After validating the breast-GPA, multivariable Cox regression and recursive partitioning analysis led to the development of the modified breast-GPA. The performances of the breast-GPA and modified breast-GPA were compared using the concordance index. In our cohort of 1,552 patients, the breast-GPA was validated as a prognostic tool for OS (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). In multivariable analysis of the breast-GPA and number of brain metastases (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; three v ≤ three), both were independent predictors of OS. We therefore developed the modified breast-GPA integrating a fourth clinical parameter. Recursive partitioning analysis reinforced the prognostic significance of these four factors. Concordance indices were 0.78 (95% CI, 0.77 to 0.80) and 0.84 (95% CI, 0.83 to 0.85) for the breast-GPA and modified breast-GPA, respectively (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). The modified breast-GPA incorporates four simple clinical parameters of high prognostic significance. This index has an immediate role in the clinic as a formative part of the clinician&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s discussion of prognosis and direction of care and as a potential patient selection tool for clinical trials.

Oncotarget, Jan 30, 2014

Accumulating evidence highlights the potential role of long non-coding RNAs (lncRNAs) as biomarke... more Accumulating evidence highlights the potential role of long non-coding RNAs (lncRNAs) as biomarkers and therapeutic targets in solid tumors. However, the role of lncRNA expression in human breast cancer biology, prognosis and molecular classification remains unknown. Herein, we established the lncRNA profile of 658 infiltrating ductal carcinomas of the breast from The Cancer Genome Atlas project. We found lncRNA expression to correlate with the gene expression and chromatin landscape of human mammary epithelial cells (non-transformed) and the breast cancer cell line MCF-7. Unsupervised consensus clustering of lncRNA revealed four subgroups that displayed different prognoses. Gene set enrichment analysis for cis- and trans-acting lncRNAs showed enrichment for breast cancer signatures driven by master regulators of breast carcinogenesis. Interestingly, the lncRNA HOTAIR was significantly overexpressed in the HER2-enriched subgroup, while the lncRNA HOTAIRM1 was significantly overexpre...

Clinical Breast Cancer, 2010

Sentinel lymph node (SLN) dissection (SLND) has largely replaced axillary lymph node dissection (... more Sentinel lymph node (SLN) dissection (SLND) has largely replaced axillary lymph node dissection (ALND) as the standard of care for lymph node staging in patients with clinically node-negative breast cancer. Multiple studies have shown that SLN status accurately predicts the status of the remaining nodes in the axillary basin, enabling the surgeon to select patients who are more likely to benefit from ALND. 1-3 This minimally invasive procedure offers an effective means of axillary staging, while significantly reducing the surgical morbidities associated with ALND and improving the overall quality of life postoperatively. Several investigators have reported that SLN identification rates are lower in older breast cancer patients. 2,6,7 In a single-institution prospective trial, Sener and colleagues reported age as a predictive factor for failure to identify SLNs in node-negative patients 70 years of age and older. 7 In addition, the National Surgical Adjuvant Breast and Bowel Project B-32 and the American College of Surgeons Oncology Group Z0010 trials reported similar results. 2,6 The reasons for lower SLN identification rates in older patients in these studies were not clearly defined. In the current study, we reviewed the technical outcomes of SLND in a large cohort of patients with breast cancer at a single institution and evaluated clinicopathologic factors that might have influenced the success of the procedure. In addition, we compared SLN identification rates in breast cancer patients 70 years and older versus patients younger than 70 years of age.

Journal of Cancer, 2014

Many phase II trials investigated the combination of Gemcitabine (G) and Vinorelbine (V) in the t... more Many phase II trials investigated the combination of Gemcitabine (G) and Vinorelbine (V) in the treatment of metastatic breast cancer (MBC) with variable outcomes. This study was conducted to explore whether this combination was effective and tolerable in MBC patients who were heavily pretreated with anthracyclines and taxanes. A phase I study was conducted first to establish the maximum tolerated dose (MTD) of the G and V combination in MBC patients. Then, a phase II study evaluated the response rates, the median time to progression (TTP), the overall survival (OS) as well as the toxicities resulting from this combination at the MTD. Nine patients were enrolled in the phase I study. The MTD was identified as 700mg/m(2) of G on days 1 and 8 in combination with 15 mg/m(2) of V on days 2 and 9, every 21 days. Twenty-one of 25 patients involved in the phase II study were evaluable for response. No complete or partial responses were achieved; 6 patients (24.0%) had stable disease and 15...

Clinical breast cancer, 2012

This retrospective analysis aimed to determine whether early dose reduction impacts the efficacy ... more This retrospective analysis aimed to determine whether early dose reduction impacts the efficacy of ixabepilone plus capecitabine in women with metastatic breast cancer (MBC). In 2 phase III trials, patients (N = 1973) with anthracycline/taxane-pretreated MBC were randomized to receive ixabepilone 40 mg/m(2) on day 1 plus capecitabine 1000 mg/m(2) twice daily (BID) on days 1 to 14 or single-agent capecitabine 1250 mg/m(2) BID on days 1 to 14 of a 3-week course. Because of the similar design and populations, data from trials were pooled to evaluate efficacy of the combination regimen among women who did or did not undergo ixabepilone dose reduction during the first 4 courses. To adjust for bias resulting from selecting patients with inherently better outcome based on longer treatment durations, these analyses were restricted to patients who received ≥ 4 courses of ixabepilone. The pooled cohort included 566 patients with measurable disease who were evaluable for efficacy. Patients wh...

Molecular cancer therapeutics, 2014

Patients with metastatic triple-negative breast cancer (TNBC) have poor treatment outcomes. We re... more Patients with metastatic triple-negative breast cancer (TNBC) have poor treatment outcomes. We reviewed the electronic records of consecutive patients with metastatic TNBC treated in phase I clinic at MD Anderson Cancer Center (Houston, TX) between Augu st 2005 and May 2012. One hundred and six patients received at least 1 phase I trial. Twelve of 98 evaluable patients (12%) had either complete response (CR; n = 1), partial response (PR; n = 7), or stable disease ≥ 6 months (SD; n = 4). Patients treated on matched therapy (n = 16) compared with those on nonmatched therapy (n = 90) had improved SD ≥ 6 months/PR/CR (33% vs. 8%; P = 0.018) and longer progression-free survival (PFS; median, 6.4 vs. 1.9 months; P = 0.001). Eleven of 57 evaluable patients (19%) treated with combination chemotherapy and targeted therapy had SD ≥ 6 months/PR/CR versus 1 of 41 evaluable patients (2%) treated on other phase I trials (P = 0.013), and longer PFS (3.0 vs. 1.6 months; P < 0.0001). Patients wit...

Surgery, 2012

BACKGROUND-The oncologic benefit of resecting liver metastases in breast cancer patients is uncle... more BACKGROUND-The oncologic benefit of resecting liver metastases in breast cancer patients is unclear. This study was performed to identify predictors of survival after hepatectomy. [1997][1998][1999][2000][2001][2002][2003][2004][2005][2006][2007][2008][2009][2010] 86 patients underwent resection of breast cancer liver metastases (BCLM). Clinicopathologic characteristics of the primary tumor, timing of metastasis development and treatment were recorded. Response to pre-hepatectomy chemotherapy was evaluated according to RECIST criteria, and the best response to chemotherapy during treatment and the response immediately before hepatectomy were noted. Univariate and multivariate analyses were performed to identify predictors of disease-free (DFS) and overall survival (OS).

Plastic and Reconstructive Surgery, 2011

The authors examined the safety of a protocol for planned skin-preserving delayed breast reconstr... more The authors examined the safety of a protocol for planned skin-preserving delayed breast reconstruction after postmastectomy radiotherapy with placement of a tissue expander for patients with locally advanced breast cancer (stages IIB and III). The authors compared 47 patients treated according to the protocol between December 2003 and May 2008 with 47 disease-stage-matched control patients who underwent standard delayed reconstruction after postmastectomy radiotherapy (no skin preservation or tissue expander) during the same period. Protocol-group complication rates were 21 percent for skin-preserving mastectomy and placement of the expander (stage 1), 5 percent for postmastectomy radiotherapy, 25 percent for expander reinflation after radiotherapy, and 24 percent for skin-preserving delayed reconstruction. The complication rate for standard delayed reconstruction was 38 percent. Tissue-expander loss rates were 32 percent overall, 9 percent for stage 1, 5 percent for postmastectomy radiotherapy, and 22 percent for reinflation. Wound-healing complications after reconstruction occurred in 3 percent of protocol-group and 10 percent of control-group patients. The median follow-up time for patients still alive at last follow-up was 40 months (range, 8.5 to 85.3 months). Three-year recurrence-free survival rates were 92 percent (95 percent CI, 83 to 100 percent) and 86 percent (95 percent CI, 76 to 98 percent) for the protocol and control groups, respectively (p = 0.87). In patients with locally advanced breast cancer, skin-preserving mastectomy with a deflated tissue expander on the chest wall during postmastectomy radiotherapy does not increase locoregional recurrence risk and is associated with lower complication rates of definitive reconstruction.

Oncology, 2009

A phase I study was initiated to determine the maximum tolerated dose (MTD) of prolonged-infusion... more A phase I study was initiated to determine the maximum tolerated dose (MTD) of prolonged-infusion gemcitabine combined with cyclophosphamide in patients with metastatic breast carcinoma (MBC). Patients with MBC were treated with gemcitabine infusion at 10 mg/m2/min and cyclophosphamide by intravenous piggyback injection, 4 h after initiation of the infusion. We treated 3-6 patients at a particular dose level until the MTD was determined. Overall, 44 patients received a total of 197 courses of therapy. Both drugs were given on days 1, 8 and 15 to 14 patients (68 courses). Delayed white blood cell recovery necessitated first protocol amendment to drop cyclophosphamide on days 8 and 15 in 9 patients (43 cycles). A second amendment was needed to drop gemcitabine on day 15 because of thrombocytopenia in 21 patients (86 courses). The dose-limiting toxicity was thrombocytopenia. The MTD of an optimal dose schedule was 800 mg/m2 gemcitabine infused at a rate of 10 mg/m2/min on days 1 and 8, and 400 mg/m2 cyclophosphamide, by intravenous piggyback injection, on day 1, 4 h after initiation of the gemcitabine infusion. The MTD can be given safely every 4 weeks to patients with MBC. Phase II studies are warranted to evaluate the clinical activity of this therapy.

Clinical Breast Cancer, 2015

Recurrence score (RS) derived from a 21-gene reverse transcriptase-polymerase chain reaction assa... more Recurrence score (RS) derived from a 21-gene reverse transcriptase-polymerase chain reaction assay is used to stratify patients with early-stage estrogen receptor-positive, HER2-normal breast cancer into 3 groups on the basis of 10-year distant metastasis risk: low, intermediate, and high. Published data are limited regarding the effect of RS on choice of adjuvant therapy for T1 breast cancer. We investigated the relationship between RS and choice of adjuvant therapy, prognosis, and benefit of chemotherapy (CT) in stage I breast cancer. We reviewed the records of 1030 patients with estrogen receptor-positive, HER2-normal stage I breast cancer and RS available. RSs were correlated with clinicopathologic characteristics, treatment, and outcome. Patients with pathologic (p)T1a, pT1b, and pT1c disease did not differ in distribution of low, intermediate, and high RS (P = .673). Overall, fewer than 10% of patients had a high RS. Histologic grade 1, nuclear grade 1, and low Ki-67 expression had only 1%, 0%, and 6% of high RSs, respectively. Among patients with intermediate RSs, 41% with pT1b and 46% with pT1c disease received CT. Among patients with intermediate RSs, for pT1b disease, distant disease-free survival (DDFS) did not differ between hormonal therapy (HT) alone and CT with HT (P = .752); for pT1c, DDFS was superior for CT with HT (P = .020). Histologic grade was the only independent prognostic factor of DDFS (P = .0007, 1 vs. 3; P = .035, 2 vs. 3); RS did not predict DDFS (P = .083, high vs. low; P = .066, intermediate vs. low). The added value of RS to known prognostic factors appears limited to patients with pT1b breast cancer. However, this study lacked long-term follow-up.

The Lancet, 2000

Docetaxel and vinorelbine as combined treatment for metastatic breast cancer can have the dose-li... more Docetaxel and vinorelbine as combined treatment for metastatic breast cancer can have the dose-limiting toxic effects of mucositis and neutropenic fever. We report unexpected ischaemic colitis in six patients associated with docetaxel-based therapy, three of whom were treated in a phase I study designed to establish the maximum tolerated dose of this combination with the prophylactic use of granulocyte-colony-stimulating factor. Between August, 1997, and December, 1998, 14 patients with metastatic breast cancer were treated with vinorelbine, docetaxel, and granulocyte-colony-stimulating factor in a phase I study. Three patients developed colitis similar to that seen in typhlitis. Three additional patients were identified during scheduled review of toxic effects in patients participating in clinical trials involving docetaxel. Three patients on combined vinorelbine and docetaxel developed colitis-like symptoms. Two patients died, one from necrotic bowel and the other from neutropenic fever and colitis. Two of the patients presented on day 7 and day 8 of chemotherapy, respectively, with neutropenic fever and abdominal pain; the third patient developed neutropenia without fever and abdominal pain on day 8. The other three patients were treated with docetaxel, docetaxel and pamidronate disodium, or docetaxel and cyclophosphamide. All three patients presented with abdominal pain on days 10, 5, and 4, respectively. One had non-neutropenic fever, another had neutropenic fever, and the third was afebrile and non-neutropenic at the time of presentation with abdominal pain. Three patients had blood in their diarrhoea, abdominal tenderness, or both. Computed tomography of the abdomen and pelvis showed features of colitis in three patients. This serious complication may result from the use of docetaxel and may be exacerbated by its combination with vinorelbine. Study of hospital-based patients treated with taxane-based chemotherapy is underway to find out the frequency of such complications.

International Journal of Radiation Oncology*Biology*Physics, 2015

We sought to determine the rate at which regional nodal ultrasonography would increase the nodal ... more We sought to determine the rate at which regional nodal ultrasonography would increase the nodal disease stage in patients with triple-negative breast cancer (TNBC) beyond the clinical stage determined by physical examination and mammography alone, and significantly affect the treatments delivered to these patients. We retrospectively reviewed the charts of women with stages I to III TNBC who underwent physical examination, mammography, breast and regional nodal ultrasonography with needle biopsy of abnormal nodes, and definitive local-regional treatment at our institution between 2004 and 2011. The stages of these patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; disease with and without ultrasonography of the regional nodal basins were compared using the Pearson χ(2) test. Definitive treatments of patients whose nodal disease was upstaged on the basis of ultrasonographic findings were compared to those of patients whose disease stage remained the same. A total of 572 women met the study requirements. In 111 (19.4%) of these patients, regional nodal ultrasonography with needle biopsy resulted in an increase in disease stage from the original stage by physical examination and mammography alone. Significantly higher percentages of patients whose nodal disease was upstaged by ultrasonographic findings compared to that in patients whose disease was not upstaged underwent neoadjuvant systemic therapy (91.9% and 51.2%, respectively; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.0001), axillary lymph node dissection (99.1% and 34.5%, respectively; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.0001), and radiation to the regional nodal basins (88.2% and 29.1%, respectively; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.0001). Regional nodal ultrasonography in TNBC frequently changes the initial clinical stage and plays an important role in treatment planning.

Journal of Geriatric Oncology, 2013

Data on chemotherapy regimens in elderly patients with metastatic breast cancer (MBC) are limited... more Data on chemotherapy regimens in elderly patients with metastatic breast cancer (MBC) are limited. The aim of this retrospective pooled analysis was to determine efficacy and safety of ixabepilone plus capecitabine versus capecitabine alone in patients with MBC aged ≥ 65 years. A total of 1973 patients with MBC previously treated with or resistant to anthracyclines and taxanes were randomized in two open-label, multinational, phase 3 studies (study 046 and study 048). Patients received ixabepilone (40 mg/m(2) as a 3-hour intravenous infusion every 3 weeks) plus oral capecitabine (1000 mg/m(2) administered twice each day), or capecitabine alone (1250 mg/m(2) twice each day). In total, 251 randomized patients were aged ≥ 65 years (ixabepilone plus capecitabine, n=116; capecitabine monotherapy, n=135). Efficacy results were consistent in patients aged &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;65 and ≥ 65 years with respect to the observed improvement in progression-free survival and objective response rate with ixabepilone plus capecitabine compared with capecitabine alone. No significant differences in overall survival between arms were observed for either subgroup. In the ixabepilone plus capecitabine arm, grade 3/4 hematologic adverse events (AEs) were similar in both subgroups except leukopenia and febrile neutropenia, which had a higher incidence in patients aged ≥ 65 years. The majority of grade 3/4 nonhematologic AEs were similar in the two subgroups, including fatigue, peripheral sensory neuropathy, and hand-foot syndrome. The combination of ixabepilone plus capecitabine maintains its efficacy in elderly patients with anthracycline and taxane pretreated MBC, with a similar safety profile to patients aged &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 65 years.