Phase III randomized trial of dose intensive neoadjuvant chemotherapy with or without G-CSF in locally advanced breast cancer: long-term results.

OBJECTIVE: To compare the pathologic complete response (pCR) rate of patients treated with 5-fluorouracil (5-FU), doxorubicin, and cyclophosphamide (FAC) versus dose-intense FAC plus G-CSF in the neoadjuvant setting and to compare the delivered dose intensity, disease-free survival (DFS) and overall survival (OS) times, and toxicity between treatment arms in patients with breast cancer. METHODS: Patients were randomized to receive preoperative FAC (5-FU, 500 mg/m(2); doxorubicin, 50 mg/m(2); cyclophosphamide, 500 mg/m(2)) every 21 days for four cycles or dose-intense FAC (5-FU, 600 mg/m(2); doxorubicin, 60 mg/m(2); cyclophosphamide, 1,000 mg/m(2)) plus G-CSF every 18 days for four cycles. RESULTS: Two hundred two patients were randomly assigned. The median follow-up was 7.5 years. Patients randomized to FAC plus G-CSF had a higher pCR rate as well as clinical complete response rate; however, these differences were not statistically different from those with the FAC arm. Patients in the FAC + G-CSF arm had a higher delivered dose intensity of doxorubicin in the neoadjuvant and adjuvant settings than those in the standard FAC arm. DFS and OS times were not significantly different between the two groups. However, the OS and DFS rates were significantly higher for patients who achieved a pCR than for those who did not. Thrombocytopenia, febrile neutropenia, and infection rates were higher in the FAC + G-CSF arm. CONCLUSIONS: A higher delivered dose intensity of doxorubicin with the FAC + G-CSF regimen did not result in a statistically significant higher pCR rate. However, patients who achieved a pCR experienced longer DFS and OS times.

Glutathione-s-transferase-pi expression in early breast cancer: association with outcome and response to chemotherapy.

Glutathione-S-transferase-pi (GST-pi) is a detoxification enzyme expressed in breast cancer; however its involvement in chemotherapy sensitivity and prognosis is not well understood. We evaluated the expression of GSTpi and its predictive role of chemotherapy response. Breast tumor samples from 166 patients at stage I/II of the disease were immunostained for GST-pi, and the expression was 96 %. There was a trend toward improved disease-free survival with high GST-pi expression (p =.09). There was a statistically non-significant association between high GST-pi expression and improved outcome with adjuvant chemotherapy (p =.055). Further studies should evaluate the role of GST-pi expression in relation to response to different chemotherapies.

Clinical features associated with a favorable outcome following neoadjuvant chemotherapy in women with localized breast cancer aged 35 years or younger.

BACKGROUND: There is scarce data on the outcome of young patients aged 35 years and younger, who have been treated with neoadjuvant chemotherapy. The aim of this study is to evaluate the impact of body mass index (BMI) and various prognostic factors on pathologic response and survival in young patients with localized breast cancer. PATIENTS AND METHODS: This is a retrospective evaluation on the outcome of 110 patients who were younger than 35 years at diagnosis and treated with neoadjuvant chemotherapy (CT). Patients were grouped in quartiles of BMI calculated prior to initiation of chemotherapy. Logistic regression analysis was performed to investigate the associations between prognostic variables including BMI and treatment outcome. The impact of prognostic factors on survival was analyzed by Kaplan-Maier and Cox regression tests. RESULTS: Body mass index was not correlated with pathologic complete response (pCR) (n = 13, 11.7%) or survival. Cox regression analysis revealed nodal pCR following neoadjuvant chemotherapy (HR 2.45, P = 0.048) and stage at diagnosis (HR1.99, P = 0.027) as significant independent prognostic factors for DFS, while recurrence was independently associated with shorter OS (HR 169, P = 0.029). CONCLUSION: Body mass index was not correlated with pCR or prognosis in young women with early breast cancer. Pathologic CR was shown to have a significant influence on DFS. Total axillary clearance may be used a surrogate variable in determining prognosis in young patients treated with neoadjuvant chemotherapy.

Prognostic value of body mass index in locally advanced breast cancer.

PURPOSE: The purpose of this retrospective study was to determine the association and prognostic value of body mass index (BMI) at the time of initial diagnosis in patients with locally advanced breast cancer (LABC). The analysis includes the subsets of inflammatory (IBC) and noninflammatory (non-IBC LABC) breast cancer. EXPERIMENTAL DESIGN: We identified 602 patients who had LABC treated on prospective clinical trials. BMI was divided into three groups: (a) < or =24.9 (normal/underweight), (b) 25.0 to 29.9 (overweight), and (c) > or =30 (obese). Kaplan-Meier product limit method was used to estimate survival outcomes. Cox proportional hazards were used to determine associations between survival and BMI and to test for an interaction between BMI and breast cancer type. RESULTS: Eighty-two percent had non-IBC LABC and 18% had IBC. Obese patients tended to have a higher incidence of IBC compared with overweight and normal/underweight groups (P = 0.01). Median follow up was 6 years for all patients. Median overall survival (OS) and recurrence-free survival (RFS) were 8.8 and 5.9 years, respectively. Patients with LABC who were obese or overweight had a significantly worse OS and RFS (P = 0.001) and a higher incidence of visceral recurrence compared with normal/underweight patients. In a multivariable model, BMI remained significantly associated with both OS and RFS for the entire cohort. The interactions between BMI and LABC subsets and between BMI and menopausal status were not statistically significant. CONCLUSION: Patients with LABC and high BMI have a worse prognosis. Evaluation of the biological factors associated with this observation can provide tools for additional therapeutic interventions.

Prognostic role of detection method and its relationship with tumor biomarkers in breast cancer: the university of Texas M.D. Anderson Cancer Center experience.

PURPOSE: To assess the effect of tumor detection method (screening versus symptom-based diagnosis) in predicting breast cancer survival and investigate how biological features of breast cancer are related to the tumor detection method. PATIENTS AND METHODS: The study population consisted of 5,481 women diagnosed with primary invasive breast cancer between 1997 and 2005 and received their treatment at The University of Texas M. D. Anderson Cancer Center. RESULTS: Patients with symptom-detected tumors had an increased risk of recurrence or death [relative risk (RR), 1.34; P = 0.006] and breast cancer-specific death (RR, 1.31; P = 0.117) than patients with screen-detected tumors after adjusting for tumor characteristics and treatments received. This relationship was especially evident among estrogen receptor (ER)-negative tumors (RR, 1.60 for breast cancer recurrence for ER-negative tumors; RR, 1.18 for ER-positive tumors). ER status and Ki-67 expression were statistically significantly associated with symptom detection rate after adjusting for patients' age, tumor stage, tumor size, and nuclear grade [odds ratio (OR) of ER negative versus ER positive, 1.35; P < 0.001; OR of Ki-67 10-30% versus <10%, 1.40; P = 0.005; OR of Ki-67 >30% versus <10%, 2.11; P < 0.001]. CONCLUSION: The method of detection was a statistically significant independent predictor of breast cancer recurrence. Information on the method of tumor detection should be collected to improve the prediction of prognosis of breast cancer patients.

Development of new cancers in patients with DCIS: the M.D. Anderson experience.

BACKGROUND: The purpose of this study was to describe clinical characteristics and outcome of mammographically and clinically detected new cancers in patients with previously diagnosed ductal carcinoma in situ (DCIS). METHOD: Our database was searched to identify patients with a primary diagnosis of DCIS. Those with prior evidence of invasive carcinoma were excluded from the analysis. Cumulative incidence of new cancers was estimated according to the method of Gray. Survival times were estimated using the Kaplan Meier product limit method. RESULTS: A total of 799 patients diagnosed and treated for DCIS were included in the analysis. Median age at diagnosis was 54 years (range 22-88 years) and median tumor size was 1.4 cm (range 0.2-15 cm). After a median follow-up of 2.9 years, 45 patients (5.6%) had a second event: 14 (31%) with in-situ and 31 (69%) with invasive disease. Median disease-free interval was 3.5 years (range 0.5-20.8 years). The majority of second events (63%) occurred in the opposite breast (P = 0.048) and the cumulative incidence at 5 years was 6.6%. Overall survival at 5 years was 97.4%; that for the second event was 76.1%. For mammography and self-palpation, respectively, the 5-year survival by method of detection of the second event was 63.2% and 100% (P = 0.08 with a 33% power to detect a difference). CONCLUSION: Second events following DCIS occurs primarily in the opposite breast and have a negative impact on survival.

Postmastectomy radiation improves the outcome of patients with locally advanced breast cancer who achieve a pathologic complete response to neoadjuvant chemotherapy.

PURPOSE: The aim of this study was to investigate the role of postmastectomy radiation therapy in women with breast cancer who achieved a pathologic complete response (pCR) to neoadjuvant chemotherapy. METHODS AND MATERIALS: We retrospectively identified 226 patients treated at our institution who achieved a pCR at surgery after receiving neoadjuvant chemotherapy. Of these, the 106 patients without inflammatory breast cancer who were treated with mastectomy were analyzed. The patients' clinical stages at diagnosis were I in 2%, II in 31%, IIIA in 30%, IIIB in 25%, and IIIC in 11% (American Joint Committee on Cancer 2003 system). Of the patients, 92% received anthracycline-based chemotherapy, and 38% also received a taxane. A total of 72 patients received postmastectomy radiation therapy, and 34 did not. The actuarial rates of local-regional recurrence (LRR) and survival of the two groups were compared using the log-rank test. RESULTS: The median follow-up of surviving patients was 62 months. Use of radiation therapy did not affect the 10-year rates of LRR for patients with Stage I or II disease (the 10-year LRR rates were 0% for both groups). However, the 10-year LRR rate for patients with Stage III disease was significantly improved with radiation therapy (7.3% +/- 3.5% with vs. 33.3% +/- 15.7% without; p = 0.040). Within this cohort, use of radiation therapy was also associated with improved disease-specific and overall survival. CONCLUSION: Postmastectomy radiation therapy provides a significant clinical benefit for breast cancer patients who present with clinical Stage III disease and achieve a pCR after neoadjuvant chemotherapy.

Circulating tumor cells in metastatic breast cancer: biologic staging beyond tumor burden.

BACKGROUND: The detection of circulating tumor cells (CTCs) predicts overall survival in patients with metastatic breast cancer (MBC). However, it is unknown whether CTCs have superior value compared with other standard prognostic factors. We compared the prognostic significance of CTCs with clinical and laboratory measures of tumor burden and phenotypic subtype of disease. PATIENTS AND METHODS: One hundred fifty-one patients with MBC evaluated between 2000 and 2006 were included in this retrospective analysis. Circulating tumor cells were isolated and enumerated in whole blood using an immunomagnetic bead system (CellSearch System). Overall survival was evaluated according to the level of CTCs (negative: <5 CTCs per 7.5 mL of blood; positive: >or=5 CTCs per 7.5 mL of blood), Swenerton score, cancer antigen 27-29 level, age (<50 years vs. >or=50 years), hormone-receptor status and HER2 status, metastatic site, and type and line of therapy. RESULTS: The median age of patients was 53 years (range, 24-88 years), and 44% of the patients had >5 CTCs. The median overall survival for negative versus positive CTCs were 29.3 months and 13.5 months, respectively (P<0.0001). In the multivariable Cox model, the detection of>or=5 CTCs demonstrated the highest hazard ratio with 2.2 times the risk of death (P=0.003). The prognostic value was independent of measure of tumor burden and type and line of therapy, and phenotypic subtype of the disease. CONCLUSION: Circulating tumor cells have superior and independent prognostic value of tumor burden and disease phenotype and might represent an important marker of tumor biology in MBC. Detection of CTCs should be considered for new staging stratification of patients with MBC.

Breast cancer treatment guidelines in older women.

PURPOSE: To determine patterns and predictors of concordance with institutional treatment guidelines among older women with breast cancer. METHODS: The study population included 1,568 patients aged 55 years and older who were treated at M.D. Anderson Cancer Center between July 1997 and January 2002 for stage I to IIIA invasive ductal and lobular breast cancer. Concordance with institutional guidelines was determined for definitive surgical therapy, radiotherapy after breast-conserving surgery, radiation therapy after mastectomy, adjuvant chemotherapy use, and adjuvant hormonal therapy use. The following variables were considered as possible modifiers of concordance: patient age, marital status, race, educational level, Eastern Cooperative Oncology Group performance status, comorbidity score, clinical stage, hormone receptor status, HER2-neu status, tumor grade, pathologic tumor size, lymphatic invasion, and number of lymph nodes involved. Logistic regression modeling was performed to determine the independent effect of each variable on guideline concordance. RESULTS: Older women were less likely to receive treatment in concordance with guidelines for definitive surgical therapy (P < .001), postlumpectomy radiation (P = .03), adjuvant chemotherapy (P < .001), and adjuvant hormonal therapy (P < .001). In multivariate analysis, age > or = 75 years predicted a deviation from guidelines for definitive surgical therapy, adjuvant chemotherapy, and adjuvant hormonal therapy. Nonwhite race was associated with decreased likelihood of adjuvant radiation therapy after breast conservation. CONCLUSION: After adjustment for comorbidity score, race, marital status, educational status, clinical stage, and tumor characteristics, increasing patient age was independently associated with decreased guideline concordance for definitive surgery, adjuvant chemotherapy, and adjuvant hormonal therapy. Future research should focus on delineating the possible reasons for guideline discordance.

Invasive lobular carcinoma classic type: response to primary chemotherapy and survival outcomes.

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

Outcome after pathologic complete eradication of cytologically proven breast cancer axillary node metastases following primary chemotherapy.

PURPOSE: Pathologic complete remission (pCR) of primary breast tumors after primary chemotherapy (PCT) is associated with higher relapse-free survival (RFS) and overall survival (OS) rates. The purpose of this study was to determine long-term outcome in patients achieving pCR of cytologically proven axillary lymph node (ALN) metastases. METHODS: Patients with cytologically documented ALN metastases were treated in five prospective PCT trials. After surgery, patients were subdivided into those with and without residual ALN carcinoma. Survival was calculated by the Kaplan-Meier method. RESULTS: Of 925 patients treated, 403 patients had cytologically confirmed ALN metastases. Eighty-nine patients (22%) achieved ALN pCR after PCT. Compared with the group without ALN pCR, 5-year OS and RFS were improved in patients achieving ALN pCR (93% [95% CI, 87.5 to 98.5] and 87% [95% CI, 79.7 to 94.3] v 72% [95% CI, 66.5 to 77.5] and 60% [95% CI, 54.1 to 65.9], respectively; P < .0001). Residual primary tumor did not affect outcome of those with ALN pCR. Combination anthracycline/taxane-based PCT resulted in significantly more ALN pCRs, although outcome after ALN pCR was not improved by taxanes. We constructed a nomogram demonstrating that patients who do not benefit from neoadjuvant anthracyclines are unlikely to benefit from subsequent taxanes. CONCLUSION: ALN pCR is associated with an excellent prognosis, even with a residual primary tumor, pointing to biologic differences between primary and metastatic cells. ALN pCR represents an early surrogate marker of long-term outcome. Response to initial PCT has important potential as a guide to subsequent therapy.

Factors predictive of distant metastases in patients with breast cancer who have a pathologic complete response after neoadjuvant chemotherapy.

PURPOSE: To identify clinicopathological factors predictive of distant metastasis in patients who had a pathologic complete response (pCR) after neoadjuvant chemotherapy (NC). METHODS: Retrospective review of 226 patients at our institution identified as having a pCR was performed. Clinical stage at diagnosis was I (2%), II (36%), IIIA (27%), IIIB (23%), and IIIC (12%). Eleven percent of all patients were inflammatory breast cancers (IBC). Ninety-five percent received anthracycline-based chemotherapy; 42% also received taxane-based therapy. The relationship of distant metastasis with clinicopathologic factors was evaluated, and Cox regression analysis was performed to identify independent predictors of development of distant metastasis. RESULTS: Median follow-up was 63 months. There were 31 distant metastases. Ten-year distant metastasis-free rate was 82%. Multivariate Cox regression analysis using combined stage revealed that clinical stages IIIB, IIIC, and IBC (hazard ratio [HR], 4.24; 95% CI, 1.96 to 9.18; P < .0001), identification of < or = 10 lymph nodes (HR, 2.94; 95% CI, 1.40 to 6.15; P = .004), and premenopausal status (HR, 3.08; 95% CI, 1.25 to 7.59; P = .015) predicted for distant metastasis. Freedom from distant metastasis at 10 years was 97% for no factors, 88% for one factor, 77% for two factors, and 31% for three factors (P < .0001). CONCLUSION: A small percentage of breast cancer patients with pCR experience recurrence. We identified factors that independently predicted for distant metastasis development. Our data suggest that premenopausal patients with advanced local disease and suboptimal axillary node evaluation may be candidates for clinical trials to determine whether more aggressive or investigational adjuvant therapy will be of benefit.

Biologic markers in axillary node-negative breast cancer: differential expression in invasive ductal carcinoma versus invasive lobular carcinoma.

PURPOSE: The objective of this study was to compare the differential expression of established histopathologic and biologic markers of proliferation, apoptosis, and angiogenesis in invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) in a group of axillary node-negative breast cancers. PATIENTS AND METHODS: Two hundred twenty patients with axillary node-negative ILC and IDC who underwent surgery at the University of Texas M. D. Anderson Cancer Center between 1978 and 1995 had tissue available for analysis. Of these, 206 (94%) had IDC and 14 (6%) had ILC. Estrogen receptors, progesterone receptors, tumor and stromal expression of vascular endothelial growth factor receptor 2, CD44, laminin-5, E-cadherin, and topoisomerase-2 were evaluated by immunohistochemical analysis. HER2/neu and alpha6beta4 integrin were evaluated by in situ hybridization. The Fisher exact test was used to calculate significant differences between ILC and IDC. Median age was 59 years. RESULTS: Invasive lobular carcinoma was more likely to occur in patients aged > 50 years. Invasive lobular carcinoma tended to be > 2 cm (50% vs. 39%), have a nuclear grade of 1/2 (100% vs. 72%), be estrogen receptor positive (93% vs. 70%), HER2/neu negative (92% vs. 68%), have high CD44 expression (31% vs. 16%), low stromal vascular endothelial growth factor receptor 2 expression (36% vs. 47%), no E-cadherin expression (0 vs. 90%), and low laminin-5 expression (15% vs. 25%), compared with IDC. CONCLUSION: Invasive lobular carcinoma and IDC might be distinct histologic types of breast cancer with different expression of biologic markers. These differences, not all being statistically significant in this small study, might generate hypotheses to develop tailored options for future systemic therapy.

p53 expression as a prognostic marker in inflammatory breast cancer.

PURPOSE: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer. Nuclear expression of p53 protein in breast cancer correlates with more aggressive tumors. We retrospectively analyze the expression of p53 as a prognostic marker to predict pathological complete response and survival in patients with IBC. EXPERIMENTAL DESIGN: Fifty-nine patients with IBC were treated from January 1994 to April 2000. Forty-eight patients were included. Diagnostic core biopsies were taken before treatment was started. Expression of hormone receptors and p53 was determined by immunohistochemistry. All patients received an anthracycline-based regimen preoperatively; 22 patients (46%) also received paclitaxel. Forty-four patients (92%) achieved an objective clinical response and underwent mastectomies. RESULTS: Median age at diagnosis was 48 years. Thirty patients (63%) had hormone receptor-negative tumors. Twenty-eight patients (58%) had p53-positive tumors, and 20 patients (42%) had p53-negative tumors. Nine patients (19%) achieved a pathological complete response. At a median follow-up of 77 months, 28 recurrences (58%) and 26 deaths (54%) had occurred. Patients with p53-positive tumors were younger (P=0.02) and tended to have lower 5-year progression-free survival rates (35% versus 55%; P=0.3) and overall survival rates (44% versus 54%; P=0.4). CONCLUSIONS: This retrospective analysis demonstrates that nuclear p53 protein expression may represent an adverse prognostic marker in IBC and may provide a valuable tool for selecting treatment for this aggressive disease.

Evaluation of paclitaxel in adjuvant chemotherapy for patients with operable breast cancer: preliminary data of a prospective randomized trial.

PURPOSE: Paclitaxel has significant antitumor activity in patients with metastaticbreast cancer who have been previously treated with or exposed to anthracycline-containing chemotherapy. In this prospective randomized trial, the role of paclitaxel was evaluated in an adjuvant setting to determine its impact on reducing the risk of recurrence in patients with operable breast cancer. EXPERIMENTAL DESIGN: Five hundred twenty-four patients were randomized to be treated either with 4 cycles of paclitaxel followed by 4 cycles of combination therapy with 5-fluorouracil, Adriamycin, and cyclophosphamide (Pac/FAC) or with 8 cycles of FAC alone. Patients with intact primary breast cancer received the initial 4 cycles of paclitaxel or 4 cycles of FAC in a neoadjuvant setting. Planned duration of therapy was the same in all patients. After completion of 8 cycles of chemotherapy, those patients who were > or =50 years and whose tumors were positive for estrogen receptors received tamoxifen for 5 years. RESULTS: Ninety-two patients have had a recurrence after a median follow-up of 60 months with a range of 5-89 months. Estimated disease-free survival at 48 months was 0.83 for FAC and 0.86 for Pac/FAC group. The difference between the two groups was not statistically significant (P = 0.09). The overall estimated hazard ratio for Pac/FAC compared with FAC derived by fitting the Cox regression model and incorporating terms for prognostic factors was 0.66. CONCLUSION: Preliminary results suggest that the addition of paclitaxel to a FAC regimen of adjuvant or neoadjuvant therapy may further reduce the risk of disease recurrence; however, differences were not statistically significant. At the time of this analysis, there have been 47 deaths. The survival data are too preliminary to permit meaningful evaluation of the impact of paclitaxel on mortality.

Paclitaxel improves the prognosis in estrogen receptor negative inflammatory breast cancer: the M. D. Anderson Cancer Center experience.

The treatment of inflammatory breast cancer includes preoperative anthracycline-based chemotherapy, surgery, and radiation therapy. In the past few years, taxanes, mainly paclitaxel, have been frequently used for preoperative chemotherapy, usually in sequence with anthracyclines. The purpose of this retrospective analysis was to determine how adding paclitaxel to anthracycline-based regimens affects prognosis. A total of 240 patients treated in 6 consecutive trials between 1973 and 2000 were included in the analysis. Group 1 (N = 178) consisted of patients treated in the first 4 trials (1973-1993) with FAC (5-fluorouracil/doxorubicin/cyclophosphamide) based regimens. Group 2 (N = 62) consisted of patients treated in the last 2 trials (1994-2000) with FAC followed by paclitaxel given every 3 weeks or given in a high-dose weekly schedule. The 2 groups differed with respect to median follow-up durations, which were 148 months (range, 85-283 months) in group 1 and 45 months (range, 21-99 months) in group 2. Estrogen receptor (ER) status was negative in 58 cases (33%) in group 1 and 40 cases (65%) in group 2. There was no difference in median age between the groups. The objective response rates (complete and partial) were similar (group 1, 74%; group 2, 82%). The median overall survival (OS) and progression-free survival (PFS) were better in the patients treated with paclitaxel, and these differences reached statistical significance in the patients with ER-negative disease (median OS: group 1, 32 months; group 2, 54 months; P = 0.03; median PFS: group 1, 18 months; group 2, 27 months; P = 0.04). It may be concluded that the addition of paclitaxel to anthracycline-based therapy resulted in a statistically significant improvement in outcome in patients with ER-negative inflammatory breast cancer.

Phase 2 trial of primary systemic therapy with doxorubicin and docetaxel followed by surgery, radiotherapy, and adjuvant chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil based on clinical and pathologic response in patients with stage IIB to III breast cancer : long-term results from the University of Texas M. D. Anderson Cancer Center Study ID97-099.

BACKGROUND: This study was performed to evaluate the outcomes of patients with locally advanced breast cancer (LABC) who were treated with a multidisciplinary approach including primary systemic chemotherapy and noncross-resistant adjuvant chemotherapy. METHODS: Patients with LABC received 4 or 6 cycles of doxorubicin and docetaxel (DT) as primary systemic chemotherapy (PST) every 21 days. Patients with adequate response underwent surgery followed by adjuvant chemotherapy according to pathologic response: complete (pCR), 2 more cycles of DT; partial (pPR), 2 more cycles of DT followed by 6 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (5-FU) (CMF); and minor (pMR), 6 cycles of CMF. Patients then received radiation and tamoxifen (hormone receptor-positive patients only). RESULTS: Eighty-eight patients were evaluable. Seventy-four patients had an adequate response to DT and were considered operable, and 72 underwent surgery. Ten patients (13.9%) achieved a pCR, 22 (30.5%) achieved a pPR, and 40 achieved a pMR (55.5%). Fourteen patients were considered nonoperable after DT and underwent salvage CMF therapy. Five of these patients underwent surgery and 1 had achieved a pCR. The estimated 5-year recurrence-free survival (RFS) rates for patients with pCR, pPR, and pMR were 80%, 77%, and 59%, respectively, and the estimated 5-year overall survival (OS) rates were 90%, 91%, and 74%, respectively. The 5-year OS rates were 82% for initially operable and 21% for initially inoperable patients (P < or = .001) CONCLUSIONS: Multidisciplinary therapy that includes PST with DT and adjuvant therapy with CMF administered according to the clinical and pathologic response is associated with high long-term RFS and OS rates in patients with LABC. Clinical or pathologic PR or CR to DT predicts improved RFS and OS.

Triple receptor-negative breast cancer: the effect of race on response to primary systemic treatment and survival outcomes.

PURPOSE: The goal of this study was to describe the effect of race on pathologic complete response (pCR) rates and survival outcomes in women with triple receptor-negative (TN) breast cancers. PATIENTS AND METHODS: Four hundred seventy-one patients with TN breast cancer diagnosed between 1996 and 2005 and treated with primary systemic chemotherapy were included. pCR was defined as no residual invasive cancer in the breast and axillary lymph nodes. Overall survival (OS) and recurrence-free survival (RFS) were estimated using the Kaplan-Meier product-limit method and compared between groups using the log-rank test. Cox proportional hazards models were fitted for each survival outcome to determine the relationship of patient and tumor variables with outcome. RESULTS: Median follow-up time was 24.5 months. One hundred patients (21.2%) were black, and 371 patients (78.8%) were white/other race. Seventeen percent of black patients (n = 17) and 25.1% of white/other patients (n = 93) achieved a pCR (P = .091). Three-year RFS rates were 68% (95% CI, 56% to 76%) and 62% (95% CI, 57% to 67%) for black and white/other patients, respectively, with no significant difference observed between the two groups (P = .302). Three-year OS was similar for the two racial groups. After controlling for patient and tumor characteristics, race was not significantly associated with RFS (hazard ratio [HR] = 1.08; 95% CI, 0.69 to 1.68; P = .747) or OS (HR = 1.08; 95% CI, 0.69 to 1.68; P = .735) when white/other patients were compared with black patients. CONCLUSION: Race does not significantly affect pCR rates or survival outcomes in women with TN breast cancer treated in a single institution under the same treatment conditions.

Clinical course of breast cancer patients with metastases limited to the liver treated with chemotherapy.

PURPOSE: The purpose of this retrospective analysis was to describe the clinical course of patients with breast cancer with liver metastases alone who were treated on doxorubicin/cyclophosphamide or taxane-containing chemotherapy protocols at the M. D. Anderson Cancer Center. PATIENTS AND METHODS: A total of 2,193 patients with metastatic breast cancer were treated on prospective clinical protocols at the University of Texas M. D. Anderson Cancer between 1973 and 2003. Among those, 132 were identified as having the liver as the first site of metastatic disease. The following information was obtained from the medical records: gender, age, race, performance status, menopausal status, hormonal receptor status, laboratory data, primary treatment, prior systemic treatment, disease-free interval, extent of metastatic disease, response to chemotherapy, site of progression, time to tumor progression, overall survival, and cause of death. RESULTS: Of the patients 62% received anthracycline-based regimens and 38% received anthracycline- and taxane-based regimens on various clinical protocols as the initial therapy for metastatic disease. The median follow-up of the patients was 52 months. The overall objective response rate was 66.4%; 16.4% of the patients achieved complete responses. The median time to progression was 14 months. Progression-free survival rates were 56% and 30% at 12 and 24 months, respectively. The median overall survival was 25 months. Sixteen patients (12.1%) survived longer than 60 months. There was a statistically inverse relation between a high lactate dehydrogenase level and achieving a complete response (P < 0.05). Age > or =50 years, extent of liver metastases, performance status, and lactate dehydrogenase and albumin levels are significantly related to progression-free survival (P < 0.05). Year of liver metastases diagnosis, extent of liver metastases, performance status, and albumin level are significantly related to overall survival (P < 0.05). CONCLUSIONS: This retrospective analysis demonstrated that patients with liver metastases only had high objective response rates and encouraging results for median survival obtained with currently available cytotoxic agents.

HER2 expression and efficacy of preoperative paclitaxel/FAC chemotherapy in breast cancer.

PURPOSE: We examined the correlation between HER2 expression and pathologic complete response (pCR) to paclitaxel/FAC (T/FAC) preoperative chemotherapy in breast cancer. PATIENTS AND METHODS: Retrospective analysis of data including 534 patients treated with preoperative T/FAC was performed. Gene expression results were available from two datasets of 132 and 286 patients, and were used to examine the co-expression of HER2 and topoisomerase II alpha (TOP2A) and microtubule associated protein tau (MAP-Tau). RESULTS: Of the 534 patients, 105 (20%) had HER2-overexpressing breast cancer. The pCR rates were 33% and 15% for patients with HER2+ and HER2- tumors (P<0.001). The 5-year relapse-free survival rates were 94% and 70% in HER2+ tumors with and without pCR (P=0.009). HER2 overexpression (odds ratio 2.3, 95%CI: 1.3-3.9, P=0.004), estrogen receptor (ER) status, grade and weekly schedule of paclitaxel were each significantly and independently associated with pCR in multivariate analysis. When patients were stratified by ER status, the pCR rates were 50% for HER2+/ER-, 30% for HER2-/ER-, 19% for HER2+/ER+, and 6% for HER2-/ER+ tumors. HER2 overexpression was associated with lower expression of MAP-tau (P=0.001 and P<0.001) and higher expression of TOP2A mRNAs (P=0.048 and P=0.001) in patients with ER+ disease. ER- cancers had low MAP-tau expression regardless of HER-status. CONCLUSION: HER2 overexpression is associated with higher rate of pCR to preoperative T/FAC chemotherapy regardless of ER status. HER2 overexpression also correlates with increased TOP2A and decreased MAP-tau expression in ER-positive cancers.