PubMed Health⌕ Search

Biomedical subjects

W Fraser Symmans

Publications and source records attributed to W Fraser Symmans.

At least 19 recordsLinked to original sources
PubMed2026

Sensitivity to Endocrine Therapy Index Predicts Benefit from Weekly Adjuvant Paclitaxel for Hormone Receptor-Positive Breast Cancer in the GEICAM/9906 Trial.

PURPOSE: To independently validate that low endocrine transcriptional activity measured by the sensitivity to endocrine therapy (SETER/PR) index in hormone receptor-positive (HR+) breast cancer predicts benefit from dose-dense paclitaxel chemotherapy within a second prospective-retrospective biomarker study. EXPERIMENTAL DESIGN: We conducted a blinded, prospective-retrospective biomarker analysis within the GEICAM/9906 trial (NCT00129922), which compared adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) followed by weekly paclitaxel (P) versus six cycles of FEC in lymph node-positive breast cancer. The SETER/PR index was measured in all available HR+/HER2- tumor RNA samples using a prespecified cut point (<0.75). The primary endpoint was the distant recurrence-free interval (DRFI); secondary endpoints were overall survival (OS) and breast cancer-specific survival (BCSS). RESULTS: Of 647 HR+/HER2- tumors, 567 (87.6%) passed assay quality control (279 FEC + P; 288 FEC). A low SETER/PR index was identified in 92 tumors (16.2%). There was a significant interaction between SETER/PR status and treatment on DRFI (P = 0.046). Among patients with a low SETER/PR index, FEC + P significantly improved DRFI [hazard ratio (HR), 0.46; 95% confidence interval (CI), 0.22-0.95; P = 0.035], with similar results after adjustment (HR, 0.48; 95% CI, 0.24-1; P = 0.049). No treatment benefit was observed for SETER/PR &#x2265;0.75 (HR, 1.02; 95% CI, 0.70-1.47; P = 0.931). Differences in OS and BCSS did not reach significance. CONCLUSIONS: Low endocrine transcriptional activity predicts benefit from adding weekly paclitaxel to anthracycline-based adjuvant chemotherapy in HR+/HER2- breast cancer. These findings independently validate the SETER/PR index as a predictive biomarker for paclitaxel-based chemotherapy and support its potential role in guiding regimen selection.

Humans↗
PubMed2026

Development and Validation of a Multimodal Clinical, Pathologic, and Genomic Model for Breast Cancer Recurrence.

PURPOSE: To develop and validate a multimodal recurrence-risk model integrating histology, genomic testing, and clinical variables. METHODS: We developed AI-Path, a whole-slide image biomarker for recurrence prediction trained in CALGB 9344, and validated it in three independent cohorts: TAILORx, a multi-site Chicago cohort, and the MDX-BRCA cohort. We then integrated AI-Path with Oncotype DX Recurrence Score (RS), tumor size, and nodal status into a Cox model, PathClinRS, fit using 60% of cases from TAILORx, with the remaining 40% held out for validation. The primary end point was distant recurrence-free interval. Performance was assessed using Harrell's concordance index (C-index) and Kaplan-Meier analyses. RESULTS: A total of 12,418 patients were included. In TAILORx, AI-Path outperformed RS for distant recurrence (C-index, 0.682 vs 0.647; P = .038), driven by superior prediction of late recurrence (0.656 vs 0.567; P < .001). In node-negative disease, PathClinRS outperformed RSClin in the TAILORx fitting (0.72 vs 0.70; P = .016) and validation sets (0.74 vs 0.70; P = .004). In node-positive disease, PathClinRS outperformed RSClinN+ in Chicago (0.94 vs 0.74; P < .001) and MDX-BRCA (0.71 vs 0.66; P = .004) cohorts. Compared with NATALEE eligibility, PathClinRS identified nearly twice as many high-risk node-negative patients while maintaining a comparable 10-year distant recurrence risk (16.7% vs 16.6% per NATALEE eligibility in TAILORx fitting; 21.0% vs 19.4% in TAILORx validation). PathClinRS identified 68% of intermediate risk premenopausal patients as low-risk with no evidence of chemotherapy benefit, compared to only 36% identified as low risk by standard clinicopathologic criteria. CONCLUSION: Digital histopathology provides prognostic information complementary to genomic assays and has the potential to personalize therapy beyond existing clinicogenomic tools.

Journal Article↗
PubMed2025

An Annotated Biobank of Triple-Negative Breast Cancer Patient-Derived Xenografts Features Treatment-Na&#xef;ve and Longitudinal Samples during Neoadjuvant Chemotherapy.

UNLABELLED: Triple-negative breast cancer (TNBC) that fails to respond to neoadjuvant chemotherapy (NACT) can be lethal. Developing effective strategies to eradicate chemoresistant disease requires experimental models that recapitulate the heterogeneity characteristic of TNBC. To that end, we established a biobank of 92 orthotopic patient-derived xenograft (PDX) models of TNBC from the tumors of 75 patients enrolled in A Robust TNBC Evaluation fraMework to Improve Survival clinical trial (ARTEMIS, NCT02276443), including 12 longitudinal sets generated from serial patient biopsies collected throughout NACT treatment and from metastatic disease. Models were established from both chemosensitive and chemoresistant tumors, and nearly 30% of the PDX models were capable of metastasizing to the lungs. Comprehensive molecular profiling demonstrated conservation of genomes and transcriptomes between patient and corresponding PDX tumors, with representation of all major transcriptional subtypes. Transcriptional changes observed in the longitudinal PDX models highlighted dysregulation in pathways associated with DNA integrity, extracellular matrix interactions, the ubiquitin-proteasome system, epigenetics, and inflammatory signaling. These alterations revealed a complex network of adaptations associated with chemoresistance. Overall, this PDX biobank provides a valuable tool for tackling the most pressing issues facing the clinical management of TNBC. SIGNIFICANCE: The development of a patient-derived xenograft biobank that comprehensively captures the genomic and transcriptional diversity of triple-negative breast cancer promises to be a robust resource to investigate and overcome chemoresistance and metastasis.

Animals↗
PubMed2025

Integration of Gene Expression and Digital Histology to Predict Treatment-Specific Responses in Breast Cancer.

Deep learning models applied to digital histology can predict gene expression signatures (GES) and offer a low-cost, rapidly available alternative to molecular testing at the time of diagnosis. We optimized transformer-based models to infer GES results and applied this approach to pre-treatment H&E-stained biopsies from 1,940 breast cancer patients treated with neoadjuvant chemotherapy in clinical trial and real-world cohorts. The most predictive histology-derived GES for pathologic complete response (pCR) in the I-SPY2 trial was validated in four external cohorts: CALGB 40601, CALGB 40603, a trial of durvalumab plus CT, and standard-of-care CT-treated patients from the University of Chicago. Among HER2-negative patients, a transformer-based model trained using a signature composed of estrogen-regulated genes, proliferation, apoptosis, and interferon response genes predicted pCR with an AUC of 0.794, outperforming models based on clinical features alone (AUC 0.704, p = 0.001), pathologist TIL assessment, and a model trained directly to predict response from I-SPY2 cases. Tertiles of this signature stratify patients into clinically relevant groups with increasing likelihood of complete response, with pCR rates &#x2265;50% in the top tertile regardless of treatment or hormone receptor status. Additional transformer-based signature models predicted response to specific therapies (but not chemotherapy alone), including a HER2 signaling signature in IO-treated patients, and a claudin-low signature in bevacizumab treated patients. In HER2- cohorts with available gene expression data and histology, models trained on expression data performed similarly to digital histology predictions, but the combination of gene expression and histology outperformed histology alone. These findings suggest that histology-based GES provides additive information to RNA sequencing data and can inform precision treatment selection across breast cancer subtypes.

Journal Article↗
PubMed2006

Accuracy of the combination of mammography and sonography in predicting tumor response in breast cancer patients after neoadjuvant chemotherapy.

BACKGROUND: Residual tumor size after neoadjuvant chemotherapy is an important consideration in surgical planning. We examined the accuracy of the combination of mammography and sonography in predicting pathologic residual tumor size. METHODS: Tumor size was evaluated by physical examination, mammography, and sonography at diagnosis and before surgery in 162 breast cancer patients who received neoadjuvant chemotherapy. Agreement between the predicted and the pathologic responses and the predicted and the pathologic tumor sizes was calculated. The effect of invasive lobular carcinoma, high nuclear grade, hormone receptor positivity, and the presence of an extensive intraductal component on the accuracy of mammography and sonography in predicting pathologic residual tumor size was analyzed. RESULTS: Forty-two patients (25.9%) had a pathologic complete response (pCR). Overall agreement between predicted and pathologic responses was 53% for physical examination, 67% for mammography plus sonography, and 63% for physical examination plus mammography and sonography. The sensitivity of mammography and sonography in predicting pCR was 78.6%, and the specificity was 92.5%; the accuracy was 88.9%. Residual tumor size determined by mammography and sonography correlated with pathologic residual tumor size (r = .662); pathologic tumor size was within .5 cm of predicted in 69.1% of patients. Multivariate analysis showed that pathologic residual tumor size was underestimated for lobular carcinoma and overestimated for poorly differentiated tumors. CONCLUSIONS: The combination of mammography and sonography has a high accuracy in predicting pCR after neoadjuvant chemotherapy. Agreement of residual tumor size in mammography and sonography with pathologic residual tumor size was moderate.

Adult↗
PubMed2006

The safety of breast-conserving surgery in patients who achieve a complete pathologic response after neoadjuvant chemotherapy.

BACKGROUND: The objectives of this study were to determine the locoregional recurrence (LRR) rate and to evaluate the correlation between surgical resection volume (RV) and LRR in patients with breast cancer who underwent segmental mastectomy after achieving a pathologic complete response (pCR) on neoadjuvant chemotherapy. METHODS: The authors reviewed the outcomes of all 109 patients who underwent segmental mastectomy after the complete eradication of invasive disease by neoadjuvant chemotherapy at their institution between 1987 and 2002. LRRs were recorded, and RVs after segmental mastectomy were calculated and categorized as small, medium, or large. RESULTS: At a median follow-up of 6.6 years, 3 patients (2.7%) developed LRR. In 2 of those patients, the recurrence was located in the ipsilateral breast; in the other patient, the recurrence was located in the supraclavicular lymph nodes with synchronous distant metastases. The median RV was 73.12 cm3 (range, 2.82-451.51 cm3). Large RVs (>125 cm3) were less common than small RVs (up to 70 cm3) or medium RVs (between 70 cm3 and 125 cm3; P = .009 and P<.0001, respectively). One patient with a small RV had an LRR at 4 years, and 2 patients with medium RVs had LLRs at 2.3 years and 6 years, respectively. The 5-year and 10-year LRR-free survival rates were 98.1% and 96.5%, respectively, and the corresponding overall survival rates were 96% and 92%, respectively. CONCLUSIONS: Segmental mastectomy was associated with excellent locoregional control in patients who achieved a pCR after neoadjuvant chemotherapy. Prospective studies are needed to examine whether decreasing the RVs in this patient population leads to an increased LRR rate.

Adult↗
PubMed2006

Pharmacogenomic predictor of sensitivity to preoperative chemotherapy with paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide in breast cancer.

PURPOSE: 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 + 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).

Adult↗
PubMed2006

Use of lymphoscintigraphy defines lymphatic drainage patterns before sentinel lymph node biopsy for breast cancer.

BACKGROUND: Lymphoscintigraphy (LSG) can identify lymphatic drainage patterns before sentinel lymph node (SLN) biopsy is performed in patients with early-stage breast cancer, but the importance of extraaxillary SLNs seen on LSG is unknown. We assessed whether drainage patterns seen on LSG were associated with histologic findings in axillary SLNs recovered at SLN biopsy. STUDY DESIGN: From a prospectively maintained database, we identified 1,201 clinically node-negative patients with invasive breast cancer who underwent preoperative LSG and axillary SLN biopsy. Patient and tumor characteristics, LSG results, and final SLN pathology results were examined. RESULTS: LSG showed drainage to internal mammary (IM) nodes in 1.6% of patients, axillary nodes in 68.1%, both IM and axillary nodes in 19.8%, and no drainage in 10.3%. Drainage to IM nodes was observed for tumors in all quadrants of the breast. Patients with IM drainage had a younger median age than patients without IM drainage (51.8 versus 58.3 years, respectively; p < 0.001). The intraoperative axillary SLN identification rate was higher when axillary drainage was observed on LSG than when it was not observed (98.7% versus 93.0%, respectively; p < 0.001), but the LSG drainage pattern was not associated with pathologic status of the SLN or number of metastatic SLNs. At a median followup of 32 months, 4 patients had regional nodal recurrence. CONCLUSIONS: Almost one-fourth of patients had lymphatic drainage to the extraaxillary lymph nodes, particularly the IM nodes, seen on LSG. Extraaxillary drainage seen on LSG did not preclude identification of axillary SLNs at operation. Longterm followup of patients with lymphoscintigraphic evidence of extraaxillary drainage is needed to determine whether regional and systemic recurrence patterns differ in these patients.

Adult↗
PubMed2006

Reproducibility of gene expression signature-based predictions in replicate experiments.

PURPOSE: The goals of this analysis were to (a) determine concordance of gene expression results from replicate experiments, (b) examine prediction agreement of multigene predictors on replicate data, and (c) assess the robustness of prediction results in the face of noise. PATIENTS AND METHODS: Affymetrix U133A gene chips were used for gene expression profiling of 97 fine-needle aspiration biopsies from breast cancer. Thirty-five cases were profiled in replicates: 17 within the same laboratory, 11 in two different laboratories, and 15 to assess manual and robotic labeling. We used data from 62 cases to develop 111 distinct pharmacogenomic predictors of response to therapy. These were tested on cases profiled in duplicates to determine prediction agreement and accuracy. To evaluate the robustness of the pharmacogenomic predictors, we also introduced random noise into the informative genes in one half of the replicates. RESULTS: The average concordance correlation coefficient was 0.978 (range, 0.96-0.99) for intralaboratory replicates, 0.962 (range, 0.94-0.98) for between-laboratory replicates, and 0.971 (range, 0.93-0.99) for manual versus robotic labeling. The mean % prediction agreement on replicate data was 97% (95% CI, 0.96-0.98; SD, 0.006), 92% (95% CI, 0.90-0.93; SD, 0.009), and 94% (95% CI, 0.92-0.95; SD, 0.008) for support vector machines, diagonal linear discriminant analysis, and k-nearest neighbor prediction methods, respectively. Mean accuracy in the test set was 77% (95% CI, 0.74-0.79; SD, 0.014), 66% (95% CI, 0.63-0.73; SD, 0.015), and 64% (95% CI, 0.60-0.67; SD, 0.016), respectively. CONCLUSION: Gene expression results obtained with Affymetrix U133A chips are highly reproducible within and across two high-volume laboratories. Pharmacogenomic predictions yielded >90% agreement in replicate data.

Biopsy, Needle↗
PubMed2006

Impact of concurrent proliferative high-risk lesions on the risk of ipsilateral breast carcinoma recurrence and contralateral breast carcinoma development in patients with ductal carcinoma in situ treated with breast-conserving therapy.

BACKGROUND: The purpose of the study was to determine the risk of ipsilateral breast carcinoma recurrence (IBCR) and contralateral breast carcinoma (CBC) development in patients with a concurrent diagnosis of ductal carcinoma in situ (DCIS) with atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), or lobular carcinoma in situ (LCIS). METHODS: Records of all 307 patients with DCIS treated with breast-conserving treatment (BCT) from 1968 to 1998 were analyzed. Initial pathology reports and all slides available were re-reviewed for evidence of ADH, ALH, or LCIS. Actuarial local recurrence rates were calculated. RESULTS: Fifty-five cases of DCIS were associated with ADH, 11 with ALH or LCIS, and 14 with both ADH and ALH or LCIS. Overall, IBCR occurred in 14% and no significant difference in the IBCR rate was identified for patients with proliferative lesions compared with patients without these lesions (P = 0.38). Development of CBC in patients with concurrent DCIS and ADH was 4.4 times (95% confidence interval [CI], 1.44-13.63) that in patients with DCIS alone (P < 0.01). The 15-year cumulative rate of CBC development was 22.7% in patients with ALH or LCIS compared with 6.5% in patients without these lesions (P = 0.30) and 19% in patients with ADH compared with 4.1% in patients with DCIS alone (P < 0.01). CONCLUSION: The risk of CBC development is higher with concurrent ADH than in patients with DCIS alone, and these patients may therefore be appropriate candidates for additional chemoprevention strategies. Concurrent ADH, ALH, or LCIS with DCIS is not a contraindication to BCT.

Breast Neoplasms↗
PubMed2006

B cell translocation gene 1 contributes to antisense Bcl-2-mediated apoptosis in breast cancer cells.

The antiapoptotic protein Bcl-2 is overexpressed in a majority of breast cancers, and is associated with a diminished apoptotic response and resistance to various antitumor agents. Bcl-2 inhibition is currently being explored as a possible strategy for sensitizing breast cancer cells to standard chemotherapeutic agents. Antisense Bcl-2 oligonucleotides represent one method for blocking the antiapoptotic effects of Bcl-2. In this study, we show that antisense Bcl-2 efficiently blocks Bcl-2 expression, resulting in the apoptosis of breast cancer cells. Antisense Bcl-2-mediated cytotoxicity was associated with the induction of the B cell translocation gene 1 (BTG1). Importantly, knockdown of BTG1 reduced antisense Bcl-2-mediated cytotoxicity in breast cancer cells. Furthermore, BTG1 expression seems to be negatively regulated by Bcl-2, and exogenous expression of BTG1 induced apoptosis. These results suggest that BTG1 is a Bcl-2-regulated mediator of apoptosis in breast cancer cells, and that its induction contributes to antisense Bcl-2-mediated cytotoxic effects.

Apoptosis↗
PubMed2006

Molecular classification of breast cancer: limitations and potential.

Reverse transcription polymerase chain reaction and DNA microarrays are increasingly used in the clinic and in clinical research as prognostic or predictive tests. Results from these tests led to novel risk stratification methods and to new molecular classification of breast cancer. Some of these tools already complement existing diagnostic tests and can aid medical decision making in some situations. Better understanding of the molecular classes of breast cancer, independent of their prognostic and predictive values, may also lead to new biological insights and eventually to better therapies that are directed toward particular molecular subsets. However, there is substantially less experience with these emerging technologies than with the more established methods, the accuracy of which is often overestimated. This review discusses some of the limitations and strengths of current gene expression-based molecular classification of breast cancer. To provide context for this discussion, we also briefly examine the performance of estrogen receptor immunohistochemistry, which represents an essential part of the routine diagnostic workup for all breast cancer patients.

Biomarkers, Tumor↗
PubMed2006

RefSeq refinements of UniGene-based gene matching improve the correlation of expression measurements between two microarray platforms.

Matching genes across microarray platforms is a critical step in meta-analysis. Standard practice uses UniGene to match genes. Numerous studies have found poor correlations between platforms when using UniGene matching. We profiled samples from 33 breast cancer patients on two different microarray platforms (Affymetrix and cDNA) and investigated gene matching. Our results confirmed that UniGene-based matching led to poor correlations of gene expression between platforms. Using RefSeq, a database maintained by the National Center for Biotechnology Information (NCBI), we developed and implemented a new method to refine gene matching. We found that the correlations between gene expression measurements were substantially higher after the RefSeq matching. Our approach differs from previously reported sequence-matching approaches and retains useful expression measurements. It is a sensible approach for matching probes across platforms. We conclude that UniGene alone is insufficient to match genes across platforms. Refined matching based on RefSeq significantly improves the quality of matches.

Breast Neoplasms↗
PubMed2005

Nomograms to predict pathologic complete response and metastasis-free survival after preoperative chemotherapy for breast cancer.

PURPOSE: To combine clinical variables associated with pathologic complete response (pCR) and distant metastasis-free survival (DMFS) after preoperative chemotherapy (PC) into a prediction nomogram. PATIENTS AND METHODS: Data from 496 patients treated with anthracycline PC at the Institut Gustave Roussy were used to develop and calibrate a nomogram for pCR based on multivariate logistic regression. This nomogram was tested on two independent cohorts of patients treated at the M.D. Anderson Cancer Center. The first cohort (n = 337) received anthracycline; the second cohort (n = 237) received a combination of paclitaxel and anthracycline PC. A separate nomogram to predict DMFS was developed using Cox proportional hazards regression model. RESULTS: The pCR nomogram based on clinical stage, estrogen receptor status, histologic grade, and number of preoperative chemotherapy cycles had good discrimination and calibration in the training and the anthracycline-treated validation sets (concordance indices, 0.77, 0.79). In the paclitaxel plus anthracycline group, when the predicted pCR rate was less than 14%, the observed rate was 7.5%; for a predicted rate of > or = 38%, the actual rate was 85%. For a predicted rate between 14% to 38%, the observed rates were 50% with weekly and 27% with 3-weekly paclitaxel. This indicates that patients with intermediate chemotherapy sensitivity benefit the most from the optimized schedule of paclitaxel. Patients unlikely to achieve pCR to anthracylines remain at low probability for pCR, even after inclusion of paclitaxel. The nomogram for DMFS had a concordance index of 0.72 in the validation set and outperformed other prediction tools (P = .02). CONCLUSION: Our nomograms predict pCR accurately and can serve as a basis to integrate future molecular markers into a clinical prediction model.

Anthracyclines↗
PubMed2005

Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer.

PURPOSE: We sought to identify gene expression markers that predict the likelihood of chemotherapy response. We also tested whether chemotherapy response is correlated with the 21-gene Recurrence Score assay that quantifies recurrence risk. METHODS: Patients with locally advanced breast cancer received neoadjuvant paclitaxel and doxorubicin. RNA was extracted from the pretreatment formalin-fixed paraffin-embedded core biopsies. The expression of 384 genes was quantified using reverse transcriptase polymerase chain reaction and correlated with pathologic complete response (pCR). The performance of genes predicting for pCR was tested in patients from an independent neoadjuvant study where gene expression was obtained using DNA microarrays. RESULTS: Of 89 assessable patients (mean age, 49.9 years; mean tumor size, 6.4 cm), 11 (12%) had a pCR. Eighty-six genes correlated with pCR (unadjusted P < .05); pCR was more likely with higher expression of proliferation-related genes and immune-related genes, and with lower expression of estrogen receptor (ER) -related genes. In 82 independent patients treated with neoadjuvant paclitaxel and doxorubicin, DNA microarray data were available for 79 of the 86 genes. In univariate analysis, 24 genes correlated with pCR with P < .05 (false discovery, four genes) and 32 genes showed correlation with P < .1 (false discovery, eight genes). The Recurrence Score was positively associated with the likelihood of pCR (P = .005), suggesting that the patients who are at greatest recurrence risk are more likely to have chemotherapy benefit. CONCLUSION: Quantitative expression of ER-related genes, proliferation genes, and immune-related genes are strong predictors of pCR in women with locally advanced breast cancer receiving neoadjuvant anthracyclines and paclitaxel.

Adult↗
PubMed2005

Breast cancer molecular subtypes respond differently to preoperative chemotherapy.

PURPOSE: Molecular classification of breast cancer has been proposed based on gene expression profiles of human tumors. Luminal, basal-like, normal-like, and erbB2+ subgroups were identified and were shown to have different prognoses. The goal of this research was to determine if these different molecular subtypes of breast cancer also respond differently to preoperative chemotherapy. EXPERIMENTAL DESIGN: Fine needle aspirations of 82 breast cancers were obtained before starting preoperative paclitaxel followed by 5-fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. Gene expression profiling was done with Affymetrix U133A microarrays and the previously reported "breast intrinsic" gene set was used for hierarchical clustering and multidimensional scaling to assign molecular class. RESULTS: The basal-like and erbB2+ subgroups were associated with the highest rates of pathologic complete response (CR), 45% [95% confidence interval (95% CI), 24-68] and 45% (95% CI, 23-68), respectively, whereas the luminal tumors had a pathologic CR rate of 6% (95% CI, 1-21). No pathologic CR was observed among the normal-like cancers (95% CI, 0-31). Molecular class was not independent of conventional cliniocopathologic predictors of response such as estrogen receptor status and nuclear grade. None of the 61 genes associated with pathologic CR in the basal-like group were associated with pathologic CR in the erbB2+ group, suggesting that the molecular mechanisms of chemotherapy sensitivity may vary between these two estrogen receptor-negative subtypes. CONCLUSIONS: The basal-like and erbB2+ subtypes of breast cancer are more sensitive to paclitaxel- and doxorubicin-containing preoperative chemotherapy than the luminal and normal-like cancers.

Adult↗
PubMed2005

Weekly paclitaxel improves pathologic complete remission in operable breast cancer when compared with paclitaxel once every 3 weeks.

PURPOSE: To determine the impact a change in schedule of paclitaxel administration from once every 3 weeks to frequent administration would have on the pathologic complete response (pCR) rate in the breast and lymph nodes for patients with invasive breast cancer treated with primary systemic chemotherapy (PST). PATIENTS AND METHODS: Patients with clinical stage I-IIIA breast cancer were randomly assigned to receive PST of paclitaxel doses administered either weekly (for a total of 12 doses of paclitaxel) or once every 3 weeks (four cycles), followed by four cycles of fluorouracil/doxorubicin/cyclophosphamide (FAC) in standard doses every 3 weeks. Two different doses of paclitaxel were used based on lymph node status defined by ultrasound and fine needle aspiration. Clinical response and extent of residual disease in the breast and lymph nodes was assessed after completion of all chemotherapy. RESULTS: A total of 258 patients were randomly assigned to receive doses of paclitaxel administered either weekly or once every 3 weeks, followed by FAC. Of these 258 patients, 110 patients had histologic lymph node involvement and 148 patients had clinical N0 disease. Weekly paclitaxel followed by FAC was administered to 127 patients and once-every-3-weeks paclitaxel followed by FAC was administered to 131 patients. Clinical response to treatment was similar between groups (P = .25). Patients receiving weekly paclitaxel had a higher pCR rate (28.2%) than patients treated with once-every-3-weeks paclitaxel (15.7%; P = .02), with improved breast conservation rates (P = .05). CONCLUSION: The change in schedule of paclitaxel from once every 3 weeks to a more frequent administration significantly improved the ability to eradicate invasive cancer in the breast and lymph nodes.

Adult↗