The impact of obesity on receipt of adjuvant chemotherapy for breast cancer in the National Comprehensive Cancer Network (NCCN) centers.

Disparities in the receipt of adjuvant chemotherapy for early stage breast cancer is an important factor influencing mortality. We investigated whether greater body mass index (BMI) decreases receipt of adjuvant chemotherapy among women with operable breast cancer. In the NCCN breast cancer outcomes database, we identified women aged ≤ 70 with newly diagnosed stage I, II, or III breast cancer between 1997 and 2007, for whom use of adjuvant chemotherapy was classified as either standard-of-care or discretionary based on their clinical characteristics. Body mass index was assessed in categories (<18.5 kg/m(2) [underweight], 18.5 to <25 kg/m(2) [normal], 25 to <30 kg/m(2) [overweight], 30-39 kg/m(2) [obese], ≥ 40 kg/m(2) [extreme obese]). Multivariable logistic regression analysis was used to examine the association between BMI and receipt of chemotherapy in each classification group. 9,527 women were eligible for the study; 40% normal weight or less; 31% overweight; 24% obese; and 5% extremely obese. In multivariable analysis, there was no significant association between BMI and receipt of chemotherapy in either classification group. Among women for whom chemotherapy would be considered standard-of-care, older age (P < 0.001), comorbidity (P < 0.001), and non-Hispanic black ethnicity (P = 0.002) were associated with a lower likelihood of receipt of chemotherapy; however, the effect of ethnicity was not modified by obesity. Among women treated for operable breast cancer in the NCCN centers, BMI had no impact on receipt of adjuvant chemotherapy and did not modify the lower likelihood of chemotherapy among non-Hispanic black patients. Further investigation is needed into other factors that contribute to patient disparities in the receipt of chemotherapy in major academic centers.

Addition of GM-CSF to trastuzumab stabilises disease in trastuzumab-resistant HER2+ metastatic breast cancer patients.

BACKGROUND: One of the proposed mechanisms of trastuzumab-induced regression of human epidermal growth factor receptor 2-positive (HER2+) tumours includes facilitation of antibody-dependent cell-mediated cytotoxicity (ADCC). Granulocyte-macrophage colony-stimulating factor (GM-CSF) mediates ADCC. We presented our pilot study of adding GM-CSF to trastuzumab in patients with trastuzumab-resistant HER2+ metastatic breast cancer. METHODS: Patients with HER2+ metastatic breast cancer that progressed after trastuzumab +/- chemotherapy were continued on trastuzumab 2 mg kg(-1) intravenous weekly and GM-CSF 250 µg m(-2) subcutaneous daily. Patients were assessed for response every 8 weeks. Treatment was continued until disease progression or intolerable toxicity. RESULTS: Seventeen patients were evaluable (median age 48 years, range 27-75 years). The median number of metastatic sites was 2 (range 1-3); the most common site was the liver (n=10). The median number of prior regimens for metastatic disease was 2 (range 1-5). No objective disease response was observed, but five patients (29%) had stable disease for a median duration of 15.8 (range 10-53.9) weeks. The most common adverse event was rash at the injection site. No grade 4 or irreversible adverse event was seen. CONCLUSION: The addition of GM-CSF to trastuzumab alone had a modest clinical benefit and acceptable safety profile in heavily pretreated patients with trastuzumab-resistant HER2+ metastatic breast cancer.

Tumour response interpretation with new tumour response criteria vs the World Health Organisation criteria in patients with bone-only metastatic breast cancer.

BACKGROUND: We compared the utility of a new response classification (MDA; based on computed tomography (CT), magnetic resonance imaging (MRI), plain radiography (XR), and skeletal scintigraphy (SS)) and the World Health Organisation response classification (WHO; based on XR and SS) in stratifying breast cancer patients with bone-only metastases with respect to progression-free survival (PFS), overall survival (OS), and clinical response. METHODS: We retrospectively reviewed 41 patients with bone-only metastatic breast cancer and assigned responses according to the MDA and WHO criteria. We analysed whether the MDA or WHO response classifications correlated with PFS and OS. RESULTS: With the MDA criteria, there were significant differences in PFS between patients classified as responders and those classified as nonresponders (P=0.025), but with the WHO criteria, there were not. Neither criteria distinguished responders from nonresponders in terms of OS. MDA response criteria correlated better than WHO response criteria with clinical response assessment. CONCLUSIONS: The MDA classification is superior to the WHO classification in differentiating between responders and nonresponders among breast cancer patients with bone-only metastases. Application of the MDA classification may allow bone lesions to be considered measurable disease. Prospective study is needed to test the MDA classification among patients with bone metastasis.

Effects of chronic hepatitis C infection on the treatment of breast cancer patients.

BACKGROUND: Although hepatitis C (HCV) is the most common blood-borne infection in the United States, little information exists about treatment of breast cancer in the setting of chronic HCV. PATIENTS AND METHODS: The databases of the University of Texas M.D. Anderson Cancer Center (MDACC) Tumor Registry, Department of Breast Medical Oncology, and Department of Laboratory Medicine were cross-referenced for patients with breast cancer, who were also identified as having HCV. Eligible patients had a diagnosis of invasive breast cancer, breast cancer treatment at MDACC, and a diagnosis of HCV. RESULTS: During chemotherapy, 25% of patients experienced elevations in aminotransferases and 44% of patients required dose reductions/delays in chemotherapy. More than 60% of the patients who received chemotherapy demonstrated a grade 2 or greater complication. However, 92% of patients were able to complete the number of cycles specified in the initial chemotherapy plan. CONCLUSIONS: As the majority of these breast cancer patients completed the initial chemotherapy plan, this study indicates that breast cancer patients with HCV can be treated with cytotoxic therapy. Comparison with historical controls showed similar rates of hepatic toxicity in the presence (or absence) of HCV, indicating that incidence of transaminitis may not be significantly affected by HCV.

Prognostic impact of discordance between triple-receptor measurements in primary and recurrent breast cancer.

BACKGROUND: We evaluated discordance in expression measurements for estrogen receptor (ER), progesterone receptor (PR), and HER2 between primary and recurrent tumors in patients with recurrent breast cancer and its effect on prognosis. METHODS: A total of 789 patients with recurrent breast cancer were studied. ER, PR, and HER2 status were determined by immunohistochemistry (IHC) and/or FISH. Repeat markers for ER, PR, and HER2 were available in 28.9%, 27.6%, and 70.0%, respectively. Primary and recurrent tumors were classified as triple receptor-negative breast cancer (TNBC) or receptor-positive breast cancer (RPBC, i.e. expressing at least one receptor). Discordance was correlated with clinical/pathological parameters. RESULTS: Discordance for ER, PR, and HER2 was 18.4%, 40.3%, and 13.6%, respectively. Patients with concordant RPBC had significantly better post-recurrence survival (PRS) than discordant cases; patients with discordant receptor status had similarly unfavorable survival as patients with concordant TNBC. IHC scores for ER and PR showed weak concordance between primary and recurrent tumors. Concordance of HER2-FISH scores was higher. CONCLUSIONS: Concordance of quantitative hormone receptor measurements between primary and recurrent tumors is modest consistent with suboptimal reproducibility of measurement methods, particularly for IHC. Discordant cases have poor survival probably due to inappropriate use of targeted therapies. However, biological change in clinical phenotype cannot be completely excluded.

A single-gene biomarker identifies breast cancers associated with immature cell type and short duration of prior breastfeeding.

The pathogenesis of breast cancers that do not express estrogen receptors or Her-2/neu receptors (ER-/HER2- phenotype) is incompletely understood. We had observed markedly elevated gene expression of gamma-aminobutyric acid type A (GABA(A)) receptor subunit pi (GABApi, GABRP) in some breast cancers with ER-/HER2- phenotype. In this study, transcriptional profiles (TxPs) were obtained from 82 primary invasive breast cancers by oligonucleotide microarrays. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to measure GABApi gene expression in a separate cohort of 121 invasive breast cancers. GABApi gene expression values from TxP and RT-PCR were standardized and compared with clinicopathologic characteristics in the 203 patients. GABApi gene expression was increased in 16% of breast cancers (13/82 TxP, 20/ 121 RT-PCR), particularly in breast cancers with ER-/HER2- phenotype (60%), and breast cancers with basal-like genomic profile (60%). The profile of genes coexpressed with GABApi in these tumors was consistent with an immature cell type. In multivariate linear regression analysis, the level of GABApi gene expression was associated with ER-/HER2- phenotype (P < 0.0001), younger age at diagnosis (P = 0.0003), and shorter lifetime duration of breastfeeding (< or = 6 months) in all women (P = 0.017) and specifically in parous women (P = 0.013). GABApi gene expression was also associated with combinations of high grade with ER-/HER2- phenotype (P = 0.002), and with Hispanic ethnicity (P = 0.036). GABApi gene expression is increased in breast cancers of immature (undifferentiated) cell type and is significantly associated with shorter lifetime history of breastfeeding and with high-grade breast cancer in Hispanic women.

Female patients with breast carcinoma age 30 years and younger have a poor prognosis: the M.D. Anderson Cancer Center experience.

BACKGROUND: The objective of this study was to analyze the outcome of treatment in young women with breast carcinoma who were treated at a single institution and to develop a clearer understanding of the natural history of the disease in these women. METHODS: One hundred eighty-five women age < or = 30 years in whom a diagnosis of invasive breast carcinoma was made between October 1985 and September 1995 were identified in the Tumor Registry data base. Patient data were obtained by chart review. All female patients with breast carcinoma who were age > 30 years and who were identified in the same data base and received treatment during the same period served as the control population. The stage-stratified overall survival (OS) rate for the study patients was compared with the OS rate for both the control population and patients in the National Cancer Data Base (NCDB). RESULTS: Of 185 patients, 11% presented with Stage I disease, 45% presented with Stage II disease, 38% presented with Stage III disease, and 6% presented with Stage IV disease. Twenty-nine percent of patients with Stage I disease received adjuvant therapy, and 84% of patients with Stage II disease and 96% of patients with Stage III disease received either adjuvant or neoadjuvant chemotherapy. Among patients with Stage I disease, 8 patients underwent mastectomy and 13 patients underwent breast-conserving surgery (BCS). Among patients with Stage II disease, 66 patients underwent mastectomy and 17 patients underwent BCS. Among patients with Stage III disease, 65 patients underwent mastectomy and 5 patients underwent BCS. The 5-year OS rate was 87% for patients with Stage I disease, 60% for patients with Stage II disease, 42% for patients with Stage III disease, and 16% for patients with Stage IV disease. Compared with the control patients and those in the NCDB, there was a trend toward worse OS rates in women age < or = 30 years. CONCLUSIONS: Women who are diagnosed with breast carcinoma at an age < or = 30 years appear to have a poorer prognosis compared with that for their older counterparts.

Fat content in individual muscle fibers of lean and obese subjects.

OBJECTIVE: To examine skeletal muscle intracellular triglyceride concentration in different fiber types in relation to obesity. DESIGN: Skeletal muscle fiber type distribution and intracellular lipid content were measured in vastus lateralis samples obtained by needle biopsy from lean and obese individuals. SUBJECTS: Seven lean controls (body mass index (BMI) 23.0+/-3.3 kg/m(2); mean+/-s.d.) and 14 obese (BMI 33.7+/-2.7 kg/m(2)) individuals; both groups included comparable proportions of men and women. MEASUREMENTS: Samples were histochemically stained for the identification of muscle fiber types (myosin ATPase) and intracellular lipid aggregates (oil red O dye). The number and size of fat aggregates as well as their concentration within type I, IIA and IIB muscle fiber types were measured. The cellular distribution of the lipid aggregates was also examined. RESULTS: The size of fat aggregates was not affected by obesity but the number of lipid droplets within muscle fibers was twice as abundant in obese compared to lean individuals. This was seen in type I (298+/-135 vs 129+/-75; obese vs lean, P<0.05), IIA (132+/-67 vs 79+/-29; P<0.05), and IIB (103+/-63 vs 51+/-13; P<0.05) muscle fibers. A more central distribution of lipid droplets was observed in muscle fibers of obese compared to lean subjects (27.2+/-5.7 vs 19.7+/-6.4%; P<0.05). CONCLUSION: The higher number of lipid aggregates and the disposition to a greater central distribution in all fiber types in obesity indicate important changes in lipid metabolism and/or storage that are fiber type-independent.

Phase I-II vinorelbine (Navelbine) by continuous infusion in patients with metastatic breast cancer: cumulative toxicities limit dose escalation.

Vinorelbine (Navelbine) has significant activity against breast carcinoma and is less neurotoxic than vinblastine. Because vinblastine has improved activity when administered by continuous infusion, we conducted a Phase I-II study to determine the maximum tolerated dose (MTD) of vinorelbine when given by continuous infusion and the response rates to it in heavily pretreated metastatic breast cancer patients. Between April 1994 and August 1997, 87 patients were entered in the study. All were female and had proven metastatic breast cancer. Ninety-five percent of them had received prior doxorubicin treatment, and 74% had received prior paclitaxel treatment. In Phase I of the study, all patients received 8 mg of vinorelbine by intravenous (i.v.) bolus followed by a continuous infusion of vinorelbine over 96 hr. When the MTD was determined, patients were entered in the Phase II arm to assess treatment responses and cumulative toxic reactions. In the Phase I arm (43 patients, 182 cycles), we determined the MTD of vinorelbine to be 8 mg by i.v. bolus followed by a continuous infusion of 11 mg/m2/day over 4 days. The dose-limiting toxic reaction was grade 3-4 granulocytopenia in 35% of the cycles and neutropenic fever in 15% of the cycles. Forty-four patients (193 cycles) were treated at the MTD. Seven (16%) of them had a response (2 complete responses, 5 partial responses). The median durations of response and survival were 4.3 and 8.6 months, respectively. However, cumulative toxic reactions (neutropenic fever and stomatitis) in 22 patients (50%) required dose reductions. A continuous infusion of vinorelbine can be safely administered but with a narrow therapeutic index because of cumulative toxic reactions. We recommend a modified MTD of vinorelbine: 8 mg by i.v. bolus followed by a continuous infusion of 10 mg/m2/day over 4 days. However, this treatment schedule offers no apparent advantage over the commonly used weekly vinorelbine schedule.

Cationic liposome-mediated E1A gene transfer to human breast and ovarian cancer cells and its biologic effects: a phase I clinical trial.

PURPOSE: Preclinical studies have demonstrated that the adenovirus type 5 E1A gene is associated with antitumor activities by transcriptional repression of HER-2/neu and induction of apoptosis. Indeed, E1A gene therapy is known to induce regression of HER-2/neu-overexpressing breast and ovarian cancers in nude mice. Therefore, we evaluated the feasibility of intracavitary injection of E1A gene complexed with DC-Chol cationic liposome (DCC-E1A) in patients with both HER-2/neu-overexpressing and low HER-2/neu-expressing breast and ovarian cancers in a phase I clinical trial. PATIENTS AND METHODS: An E1A gene complexed with DCC-E1A cationic liposome was injected once a week into the thoracic or peritoneal cavity of 18 patients with advanced cancer of the breast (n = 6) or ovary (n = 12). RESULTS: E1A gene expression in tumor cells was detected by immunohistochemical staining and reverse transcriptase-polymerase chain reaction. This E1A gene expression was accompanied by HER-2/neu downregulation, increased apoptosis, and reduced proliferation. The most common treatment-related toxicities were fever, nausea, vomiting, and/or discomfort at the injection sites. CONCLUSION: These results argue for the feasibility of intracavitary DCC-E1A administration, provide a clear proof of preclinical concept, and warrant phase II trials to determine the antitumor activity of the E1A gene.

Capecitabine for 5-fluorouracil-resistant brain metastases from breast cancer.

We report a case in which brain metastases originating from breast cancer responded to treatment with oral capecitabine. The metastases had progressed and Karnofsky performance status deteriorated despite whole brain irradiation, hormonal treatment, and systemic chemotherapy that included 5-fluorouracil (5-FU). In contrast, 2 months of treatment with oral capecitabine produced a partial response, documented by lesion size on magnetic resonance imaging and an improvement in performance status; both measures continued to improve during 11 months of capecitabine treatment.

The evolving role of bisphosphonates.

Bisphosphonates, analogs of pyrophosphate, bind to bone at sites of active bone remodeling. In clinical settings of rapid bone turnover and/or excessive osteolytic activity, they have been shown to have beneficial clinical effects. These settings include Paget's disease of bone, osteoporosis from a variety of clinical causes, and malignant bone disease. Bisphosphonate inhibition of osteolysis in cancer has been shown to be effective therapy for malignancy-associated hypercalcemia and as adjunctive therapy for the delay or prevention of cancer-related skeletal morbidity, including bone pain, pathologic fractures, and need for radiation therapy. Animal models of bone metastasis prevention by bisphosphonate treatment have provided the preclinical background for the adjuvant use of bisphosphonates in primary cancers. The success of these clinical trials has provided strong impetus for new research on bone disease and malignancy, as well as the development and testing of new and more potent bisphosphonates. Semin Oncol 28:284-290.

The influence of pathologic tumor characteristics on locoregional recurrence rates following mastectomy.

PURPOSE: The objective of this study was to evaluate the influence of pathologic factors other than tumor size and number of involved axillary nodes on the risk of locoregional recurrence (LRR) following mastectomy. PATIENTS AND METHODS: We reviewed the medical records of 1031 patients treated with mastectomy and doxorubicin-based chemotherapy without radiation on 5 prospective clinical trials. Median follow-up was 116 months (range, 6-262 months). RESULTS: Patients with gross multicentric disease were at increased risk of LRR (37% at 10 years). However, patients with multifocal disease and those with microscopic multicentric disease did not experience higher rates of LRR than those with single lesions (17% at 10 years). Patients with lymph-vascular space invasion (LVSI) or involvement of the skin or nipple also experienced high rates of LRR (25%, 32%, and 50%, respectively). The presence of close (<5 mm) or positive margins was associated with an increased risk of LRR (45%). The increased risk of LRR observed for patients with pectoral fascial invasion (33%) was not reduced when negative deep margins were obtained. On multivariate analysis, the presence of 4 or more involved axillary nodes, tumor size of greater than 5 cm, close or positive surgical margins, and gross multicentric disease were found to be independent predictors of LRR (all, p < 0.01). In a separate analysis including only patients with 1-3 involved axillary nodes, microscopic invasion of the skin or nipple, pectoral fascial invasion, and the presence of close or positive margins were significant predictors of LRR. CONCLUSION: In addition to the extent of primary and nodal disease, other factors that predict for high rates of LRR include the presence of LVSI, involvement of the skin, nipple or pectoral fascia, close or positive margins, or gross multicentric disease. These factors predict for high LRR rates regardless of the number of involved axillary nodes.

Recursive partitioning analysis of locoregional recurrence patterns following mastectomy: implications for adjuvant irradiation.

PURPOSE: Postmastectomy irradiation improves overall survival for breast cancer patients at high risk for locoregional recurrence (LRR). The objective of this study was to use recursive partitioning analysis (RPA) to define patient subgroups at high risk for LRR following mastectomy. PATIENTS AND METHODS: A cohort of 1031 patients treated on prospective trials with mastectomy and doxorubicin-based chemotherapy without irradiation was analyzed. The variables considered in the RPA were tumor size, number of involved nodes, number of nodes examined, and percentage of nodes involved (nodes involved/nodes examined). The endpoint was LRR +/- distant metastasis. Only patients with complete data were analyzed (n = 913). Median follow-up was 8 years (range, 0.7-22 years). RESULTS: Involvement of 20% or more of the lymph nodes examined was the most significant variable predicting LRR. Three risk categories were defined. Patients with 20% or more involved nodes and tumors of 3.5 cm or more were at greatest risk for LRR (41% at 8 years). An intermediate-risk group included patients with 20% or more involved nodes and tumors of less than 3.5 cm as well as those with less than 20% involved nodes and tumor size of 5 cm or greater (18% at 8 years). Patients with less than 20% involved nodes and tumor size of less than 5 cm were at lowest risk for LRR (10% at 8 years). CONCLUSION: Tumor size and extent of nodal involvement play interrelated roles in predicting LRR following mastectomy and systemic therapy. Patients with 20% or greater involved nodes and those with less than 20% nodes and tumors of 5.0 cm or greater are at significant risk of LRR and should be considered for postoperative irradiation.

Phase I study of a third-generation selective estrogen receptor modulator, LY353381.HCL, in metastatic breast cancer.

PURPOSE: We conducted this phase I trial to determine the safety and toxicity profile of LY353381.HCl-a novel, potent, third-generation selective estrogen receptor modulator (SERM)-because this benzothiophene derivative demonstrated an SERM profile in preclinical studies. PATIENTS AND METHODS: We studied 32 patients with recurrent or metastatic breast cancer. Patients were treated in four cohorts with oral daily doses of 10, 20, 50, and 100 mg. Pharmacokinetic sampling was performed during the first 72 hours following the first dose on day 1 and during the 24 hours after the day 57 dose. Eligibility criteria included Eastern Cooperative Oncology Group performance status of 0 to 2; no significant major organ dysfunction; and at least 3 weeks elapsed since most recent hormonal therapy, chemotherapy, and estrogen replacement therapy. RESULTS: The median patient age was 56 years (range, 30 years to 76 years). The median number of prior chemotherapies for metastatic disease was one (range, zero to four), while the median number of prior hormone regimens for metastatic disease was two (range, zero to five). Receptor status was estrogen receptor (ER) positive and progesterone receptor (PR) positive, 19 patients; ER positive and PR negative, eight patients; ER positive and PR unknown, two patients; and ER and PR unknown, three patients. Dose-limiting toxicity was not observed. Treatment was well tolerated with mild to moderate hot flashes in 18 of 32 patients (56%) at all dose levels. Transvaginal ultrasound performed at baseline and after 12 weeks of treatment showed no endometrial thickening. Of the 32 patients evaluable for response, six patients had stable disease for at least 6 months with a median duration of 7.7 months (range, 6.2 months to 33.8 months). The pharmacokinetics of LY353381.HCl were generally linear with respect to time and studied dose range. CONCLUSION: As predicted in preclinical testing, daily oral LY353381.HCl is safe, is well tolerated at all tested dose levels, and may be clinically beneficial in patients with extensively pretreated metastatic breast cancer. Further studies with LY353381 to evaluate the efficacy in patients with or without prior exposure to tamoxifen and fewer overall prior regimens are under way.

Phase I study of stealth liposomal doxorubicin in combination with gemcitabine in the treatment of patients with metastatic breast cancer.

PURPOSE: We conducted a single-institution phase I clinical trial to determine the maximum-tolerated dose (MTD) and define the toxic effects of stealth liposomal doxorubicin in combination with gemcitabine in patients with metastatic breast cancer. PATIENTS AND METHODS: Patients were eligible if they had disease progression with no limit on prior number of chemotherapy regimens. Prior treatment with liposomal doxorubicin and/or gemcitabine was not allowed. The starting dose of liposomal doxorubicin was 20 mg/m(2) on day 1 only with a 20% dose escalation of the previous mg/m(2) dose until MTD was reached. Gemcitabine was given as a fixed dose of 800 mg/m(2) on days 1 and 8 every 3 weeks. RESULTS: We treated 27 patients of whom six had never received chemotherapy for their disease. Most had had visceral involvement as their dominant site of disease. The dose-limiting toxicity was myelosuppression, which included neutropenia and thrombocytopenia. However, neither neutropenic fever nor episodes of bleeding were major occurrences. Significant antitumor activity was also observed with a total of two complete and seven partial responses. The recommended phase II dose is liposomal doxorubicin 24 mg/m(2) on day 1 and gemcitabine 800 mg/m(2) on days 1 and 8 every 21 days. CONCLUSION: The combination of liposomal doxorubicin and gemcitabine is an active and well tolerated regimen when administered on a 21-day schedule. Myelosuppression limited further dose escalation, however, it did not increase the incidence of neutropenic fever. Significant antitumor activity seen in heavily and minimally pretreated patients warrants further evaluation of this combination.

Breast cancer during pregnancy.

The care of a pregnant breast cancer patient is a challenging clinical situation that historically has placed the welfare of the mother in conflict with that of the fetus. For the woman in this situation, the emotions usually associated with pregnancy can be overshadowed by the emotions aroused by a diagnosis of breast cancer and its subsequent treatment. The majority of published information on the management of breast cancer during pregnancy has consisted of retrospective chart reviews, case reports, and anecdotes. There is a paucity of published data from the prospective study of women who are pregnant at the time of their breast cancer diagnosis. This review will endeavor to address the diagnosis, staging, and subsequent treatment of breast cancer during pregnancy. The limited information available for this group of women on the outcomes of labor, delivery, and neonatal health will also be reviewed. This review will not specifically address pregnancy that occurs after diagnosis and subsequent treatment for breast cancer. However, some data, particularly those of an epidemiologic nature, address breast cancer diagnosed during pregnancy or within the year following delivery.

Long-term results of combined-modality therapy for locally advanced breast cancer with ipsilateral supraclavicular metastases: The University of Texas M.D. Anderson Cancer Center experience.

PURPOSE: To determine outcomes in local-regional control, disease-free survival, and overall survival in patients with locally advanced breast cancer (LABC) who present with ipsilateral supraclavicular metastases and who are treated with combined-modality therapy. PATIENTS AND METHODS: Seventy patients with regional stage IV LABC, which is defined by our institution as LABC with ipsilateral supraclavicular adenopathy without evidence of distant disease, received treatment on three prospective trials of neoadjuvant chemotherapy. All patients received neoadjuvant chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil, or cyclophosphamide, doxorubicin, vincristine, and prednisone. Patients then received local therapy that consisted of either total mastectomy and axillary lymph node dissection (ALND) or segmental mastectomy and ALND before or after irradiation. Patients with no response to neoadjuvant chemotherapy were treated with surgery and/or radiotherapy. After completion of local therapy, chemotherapy was continued for four to 15 cycles, followed by radiotherapy. Patients older than 50 years who had estrogen receptor-positive tumors received tamoxifen for 5 years. RESULTS: Median follow-up was 11.6 years (range, 4.8 to 22.6 years). Disease-free survival rates at 5 and 10 years were 34% and 32%, respectively. The median disease-free survival was 1.9 years. Overall survival rates at 5 and 10 years were 41% and 31%, respectively. The median overall survival was 3.5 years. The overall response rate (partial and complete responses) to induction chemotherapy was 89%. No treatment-related deaths occurred. CONCLUSION: Patients with ipsilateral supraclavicular metastases but no other evidence of distant metastases warrant therapy administered with curative intent, ie, combined-modality therapy consisting of chemotherapy, surgery, and radiotherapy. Patients with ipsilateral supraclavicular metastases should be included in the stage IIIB category of the tumor-node-metastasis classification because their clinical course and prognosis are similar to those of patients with stage IIIB LABC.

NCCN: Breast cancer.

The 2001 NCCN Breast Cancer Guidelines reflect the results of 5 generations of NCCN Breast Cancer Guidelines. Evidence-based guidelines, such as the NNCN Breast Cancer Guidelines, are possible only because of the availability of high-level evidence at multiple decision points in treatment. The continued performance of high quality clinical trials is central to our ability to further improve the treatment of breast cancer. The panel believes that participation in high quality clinical trials is the preferred treatment at all points in breast cancer therapy.

Locoregional recurrence patterns after mastectomy and doxorubicin-based chemotherapy: implications for postoperative irradiation.

PURPOSE: The objective of this study was to determine locoregional recurrence (LRR) patterns after mastectomy and doxorubicin-based chemotherapy to define subgroups of patients who might benefit from adjuvant irradiation. PATIENTS AND METHODS: A total of 1,031 patients were treated with mastectomy and doxorubicin-based chemotherapy without irradiation on five prospective trials. Median follow-up time was 116 months. Rates of isolated and total LRR (+/- distant metastasis) were calculated by Kaplan-Meier analysis. RESULTS: The 10-year actuarial rates of isolated LRR were 4%, 10%, 21%, and 22% for patients with zero, one to three, four to nine, or >/= 10 involved nodes, respectively (P <.0001). Chest wall (68%) and supraclavicular nodes (41%) were the most common sites of LRR. T stage (P <.001), tumor size (P <.001), and >/= 2-mm extranodal extension (P <.001) were also predictive of LRR. Separate analysis was performed for patients with T1 or T2 primary disease and one to three involved nodes (n = 404). Those with fewer than 10 nodes examined were at increased risk of LRR compared with those with >/= 10 nodes examined (24% v 11%; P =.02). Patients with tumor size greater than 4.0 cm or extranodal extension >/= 2 mm experienced rates of isolated LRR in excess of 20%. Each of these factors continued to significantly predict for LRR in multivariate analysis by Cox logistic regression. CONCLUSION: Patients with tumors >/= 4 cm or at least four involved nodes experience LRR rates in excess of 20% and should be offered adjuvant irradiation. Additionally, patients with one to three involved nodes and large tumors, extranodal extension >/= 2 mm, or inadequate axillary dissections experience high rates of LRR and may benefit from postmastectomy irradiation.