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.

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.

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.

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.

Relationship between obesity and pathologic response to neoadjuvant chemotherapy among women with operable breast cancer.

PURPOSE: To understand the mechanism through which obesity in breast cancer patients is associated with poorer outcome, we evaluated body mass index (BMI) and response to neoadjuvant chemotherapy (NC) in women with operable breast cancer. PATIENTS AND METHODS: From May 1990 to July 2004, 1,169 patients were diagnosed with invasive breast cancer at M. D. Anderson Cancer Center and received NC before surgery. Patients were categorized as obese (BMI >or= 30 kg/m(2)), overweight (BMI of 25 to < 30 kg/m(2)), or normal/underweight (BMI < 25 kg/m(2)). Logistic regression was used to examine associations between BMI and pathologic complete response (pCR). Breast cancer-specific, progression-free, and overall survival times were examined using the Kaplan-Meier method and Cox proportional hazards regression analysis. All statistical tests were two-sided. RESULTS: Median age was 50 years; 30% of patients were obese, 32% were overweight, and 38% were normal or underweight. In multivariate analysis, there was no significant difference in pCR for obese compared with normal weight patients (odds ratio [OR] = 0.78; 95% CI, 0.49 to 1.26). Overweight and the combination of overweight and obese patients were significantly less likely to have a pCR (OR = 0.59; 95% CI, 0.37 to 0.95; and OR = 0.67; 95% CI, 0.45 to 0.99, respectively). Obese patients were more likely to have hormone-negative tumors (P < .01), stage III tumors (P < .01), and worse overall survival (P = .006) at a median follow-up time of 4.1 years. CONCLUSION: Higher BMI was associated with worse pCR to NC. In addition, its association with worse overall survival suggests that greater attention should be focused on this risk factor to optimize the care of breast cancer patients.

Residual risk of breast cancer recurrence 5 years after adjuvant therapy.

There is limited prognostic information to identify breast cancer patients who are at risk for late recurrences after adjuvant or neoadjuvant systemic therapy (AST). We evaluated the residual risk of recurrence and prognostic factors of 2838 patients with stage I-III breast cancer who were treated with AST between January 1, 1985, and November 1, 2001, and remained disease free for 5 years. Residual recurrence-free survival was estimated from the landmark of 5 years after AST to date of first recurrence or last follow-up using the Kaplan-Meier method. The log-rank test (two-sided) was used to compare groups. Residual recurrence-free survival rates at 5 and 10 years were 89% and 80%, respectively, and 216 patients developed a recurrence event. The 5-year residual risks of recurrence for patients with stage I, II, and III cancers were 7% (95% confidence interval [CI] = 3% to 15%), 11% (95% CI = 9% to 13%), and 13% (95% CI = 10% to 17%), respectively (P = .02). In multivariable analysis, stage, grade, hormone receptor status, and endocrine therapy were associated with late recurrences. Breast cancer patients have a substantial residual risk of recurrence, and selected tumor characteristics are associated with late recurrences.

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.

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 value of initial clinical disease stage after achieving pathological complete response.

The aim of this retrospective study was to determine the prognostic impact of initial clinical stage in patients who achieved a pathological complete response (pCR) after receiving primary systemic chemotherapy (PST). Between 1977 and 2006, 489 patients who had achieved a pCR after receiving an anthracycline-based PST regimen were identified. Recurrence-free survival (RFS) and overall survival (OS) were estimated with the Kaplan-Meier product limit method and the differences between groups were compared using the log-rank statistic. Cox proportional hazards models were fit to determine the association of initial clinical stage with survival outcomes after adjusting for patient and tumor characteristics. The median age was 47 years. Twenty (4.1%) patients had stage I disease, 243 (49.7%) had stage II disease, 189 (38.7%) had stage III disease, and 37 (7.5%) had inflammatory breast cancer (IBC). At a median follow-up of 45 months, 59 (12%) patients had experienced disease recurrence. The 5-year RFS and OS rates for the whole cohort were 87.8% and 89.3%, respectively. Lower clinical stage at diagnosis was associated with statistically significant higher RFS and OS rates. In a multivariate model, patients with clinical stage IIIB/C disease and those with IBC had lower RFS rates than patients with clinical stage I/II/IIIA disease. In addition, patients with clinical stage IIIB/C disease and those with IBC had a greater hazard of death than patients with clinical stage I/II/IIIA disease. Overall, patients who achieved a pCR had a low rate of recurrence. However, higher clinical stage and IBC were associated with worse outcomes in breast cancer patients who achieved a pCR after PST.

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.

Prognostic significance of HER-2 status in women with inflammatory breast cancer.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer with poorly understood prognostic variables. The purpose of this study was to define the prognostic impact of HER-2 status on survival outcomes of patients with IBC. METHODS: In all, 179 patients with IBC, diagnosed between 1989 and 2005, with known HER-2 status, and treated with an anthracycline-based chemotherapy regimen without trastuzumab, were included in the analysis. Patients with HER-2-positive disease who received trastuzumab at the time of disease recurrence were included. Survival outcomes were estimated by the Kaplan-Meier product limit method and compared across groups using the log-rank statistic. A Cox proportional hazards model was fitted to determine the association of survival outcomes with HER-2 status after adjusting for patient and tumor characteristics. RESULTS: A total of 111 patients (62%) had HER-2-negative disease and 68 (38%) had HER-2-positive disease. The median follow-up among all patients was 35 months. At the time of the analysis, 62 patients (55.9%) with HER-2-negative disease and 42 patients (61.8%) with HER-2-positive disease had a recurrence. Thirty-one patients (73.8%) with HER-2-positive disease who had a disease recurrence went on to receive trastuzumab. On univariate analysis, no statistically significant difference was observed for either recurrence-free survival (P = .75) or overall survival (P = .24) between patients who had HER-2-positive disease and those who had HER-2-negative disease. In a multivariate model, HER-2 status did not appear to significantly affect recurrence-free survival (hazards ratio [HR] of 0.75; 95% confidence interval [95% CI], 0.46-1.22 [P = .241]). In the multivariate model, patients with HER-2-positive disease had a decreased hazard of death (HR of 0.56; 95% CI, 0.34-0.93 [P = .024]) compared with patients with HER-2-negative disease. CONCLUSIONS: HER-2 status, in the absence of trastuzumab, did not appear to significantly affect recurrence-free survival. After adjusting for other characteristics, the addition of trastuzumab in the metastatic setting significantly improved survival in the HER-2-positive group above and beyond that of the HER-2-negative group. This gives us further insight into the biology of this aggressive disease and underlines the major effect of targeted intervention.

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.

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.

Clinicopathologic characteristics and prognostic factors in 420 metastatic breast cancer patients with central nervous system metastasis.

BACKGROUND: Breast cancer is the second most common cause of central nervous system (CNS) metastases. Several risk factors for CNS metastases have been reported. The objective of the current study was to describe clinicopathologic characteristics and prognostic factors in breast cancer patients with CNS metastases. METHODS: The authors retrospectively evaluated clinical data from 420 patients who had been diagnosed with breast cancer and CNS metastasis between 1994 and 2004 at the University of Texas M. D. Anderson Cancer Center. RESULTS: The median age of the patients at the time of diagnosis of breast cancer was 45 years (range, 25-77 years). Premenopausal and postmenopausal patients were distributed equally. Most patients had invasive ductal histology (91.2%), grade 3 tumors (81.4%) (using the modified Black nuclear grading system), T2 tumor classification (40.1%), and N1 lymph node status (59.7%) diagnosis. Forty percent of patients had estrogen receptor (ER)-positive disease, and 34% had progesterone receptor-positive disease. HER-2/neu status was recorded for only 248 patients, and 39% of the patients in that group had HER-2/neu-positive disease. The most common sites of first metastasis were liver, bone, and lung. CNS metastasis was the site of first recurrence in 53 patients (12%). In total, 329 patients had received either neoadjuvant treatment (113 patients) or adjuvant chemotherapy (216 patients). The majority of those patients (74.4%) had received anthracycline-based regimens. Metastasis was solitary in 111 patients (26.4%), and 29 patients had only leptomeningeal metastases. The median time from breast cancer diagnosis to CNS metastasis was 30.9 months (range, from -5 months to 216.7 months). The median follow-up after a diagnosis of CNS metastasis was 6 months (range, 7-95.9 months). In all, 359 patients died, and the overall median survival was 6.8 months. Only age at diagnosis and ER status were associated significantly with overall survival in the multivariate analysis. CONCLUSIONS: The current results indicated that the prognosis remains patients with breast cancer metastatic to the CNS. More effective treatment approaches are needed for patients with CNS metastases, even for those with favorable prognostic factors, such as ER-positive tumors or younger age.

Inflammatory breast cancer (IBC) and patterns of recurrence: understanding the biology of a unique disease.

BACKGROUND: Inflammatory breast cancer (IBC) is the most aggressive manifestation of primary breast cancer. The authors compared the prognostic features of IBC and non-IBC locally advanced breast cancer (LABC) to gain insight into the biology of this disease entity. METHODS: This retrospective analysis consisted of 1071 patients, comprising 240 patients with IBC and 831 patients with non-IBC LABC who were enrolled in 10 consecutive clinical trials (5 from each disease group). All patients received similar multidisciplinary treatment. The authors measured time to disease recurrence for each individual site from the start of treatment to the date of disease recurrence or last follow-up (recurrence-free survival) and overall survival rates to the date of last follow-up or death. RESULTS: The median follow-up period was 69 months (range, 1-367 months). Pathologically complete response rates were 13.9% and 11.7% in the IBC and non-IBC LABC groups, respectively (P = .42). The 5-year estimates of cumulative incidence of recurrence were 64.8 % and 43.4% (P < .0001), respectively, for IBC and non-IBC LABC. IBC had significantly higher cumulative incidence of locoregional recurrence and distant soft-tissue and bone disease. The 5-year overall survival (OS) rate was 40.5% for the IBC group (95% CI, 34.5%-47.4%) and 63.2% for the non-IBC LABC group (95% CI, 60.0%-66.6%; P < .0001). CONCLUSIONS: IBC was associated with a worse prognosis and a distinctive pattern of early recurrence compared with LABC. These data suggested that investigating factors affecting "homing" of cancer cells may provide novel treatment strategies for IBC.

Efficacy and safety of neoadjuvant trastuzumab combined with paclitaxel and epirubicin: a retrospective review of the M. D. Anderson experience.

BACKGROUND: A previously published prospective randomized phase 3 trial showed that administration of 24 weeks of primary systemic chemotherapy (PST) with paclitaxel and FEC(75) (fluorouracil, epirubicin, cyclophosphamide) concurrently with trastuzumab in patients with HER2-positive primary breast cancer resulted in a 60% pathologic complete response rate (PCR) with no associated severe cardiac toxicity. The purpose of this study was to review the efficacy and safety of a similar regimen outside the setting of a clinical trial. METHODS: Patients with HER2-positive breast cancer (defined as either immunohistochemical 3+ or fluorescence in situ hybridization-positive) that had received 24 weeks of neoadjuvant trastuzumab concurrently with taxane and anthracycline-based chemotherapy between 2004 and 2006 were included in the analysis. PST chemotherapy consisted of paclitaxel (80 mg/m(2)) weekly for 12 weeks followed by 4 cycles of FEC(75) (500 mg/m(2), 75 mg/m(2), and 500 mg/m(2), respectively). RESULTS: Forty patients were identified. The median age was 48 years (range, 29-81). In all, 60% of patients had stage III disease and 4 had inflammatory breast cancer. The PCR rate was 55% (95% confidence interval [CI], 38.5%-70.7%). At a median follow-up of 19 months. 5 patients had a recurrence, of which 4 did not achieve a PCR. No severe cardiac events were observed. CONCLUSIONS: Stage II and III HER2-positive breast cancer patients achieved a high rate of PCR with trastuzumab given concurrently with paclitaxel and FEC(75) chemotherapy. No severe cardiac events were observed with the regimen. The data concur with the results of a previously published trial.

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.

Are there racial differences in breast cancer treatments and clinical outcomes for women treated at M.D. Anderson Cancer Center?

PURPOSE: To determine the influence of race on breast cancer treatment and on recurrence and breast cancer specific death. PATIENTS AND METHODS: The study population consisted of 6,054 African-American or white women who were diagnosed with breast cancer and received at least one of the treatments including mastectomy or breast conservative surgery, radiation, adjuvant chemotherapy, neo-adjuvant chemotherapy, and adjuvant endocrine therapy at M.D. Anderson Cancer Center between June 1997 and February 2005. The clinical outcomes were disease-free survival and breast-cancer-specific survival. Logistic regression analysis was performed to investigate if race was associated with the selection of each primary treatment while adjusting for tumor characteristics at diagnosis. Cox proportional hazards model was used to determine the effect of race on recurrence-free survival and breast-cancer-specific survival controlling for tumor characteristics, presence of co-morbidity conditions and use of these treatments. RESULTS: The use of any primary treatment for breast cancer was not significantly different by race after adjusting for tumor characteristics and co-morbidity conditions. Although tumor characteristics at diagnosis explained the major differences in clinical outcomes, race remained an independent prognostic factor for breast-cancer-specific survival (P=0.002), and a marginally significant factor for disease-free survival (P=0.063) in multivariate analyses. CONCLUSION: Equal treatment may not lead to equal clinical outcomes given similar tumor characteristics at diagnosis. To reduce racial differences in breast cancer recurrence and survival, it is important to have a better understanding of differences in tumor biology by race and to promote the use of early detection programs among African-American women.