Breast Neoplasms: Glick J

Harris EE, Schultz D, Bertsch H, Fox K, Glick J, Solin LJ. · Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA 19104, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #12654428 No free full text.

Abstract: PURPOSE: To evaluate the long-term outcome of combined modality therapy for inflammatory breast cancer. METHODS AND MATERIALS: The data from 54 women treated between 1983 and 1996 for inflammatory breast cancer were analyzed. Patients with metastatic disease or disease progression on induction chemotherapy were excluded. Induction chemotherapy was given to 52 patients. Mastectomy was performed in 52 patients. Radiotherapy was delivered to the breast or chest wall and regional lymph nodes in all patients. The median follow-up for all patients was 5.1 years. RESULTS: The 5- and 10-year overall survival rate was 56% and 35%, respectively; the corresponding relapse-free survival rates were 49% and 34%. Patients with a pathologic complete response after chemotherapy with or without preoperative radiotherapy had better 5- and 10-year overall survival rates (65% and 46%, respectively) and 5- and 10-year relapse-free survival rates (59% and 50%, respectively) compared with patients without a pathologic complete response. Those patients had a 5- and 10-year relapse-free survival rate of 45% and 27%, respectively. Locoregional failure at 5 and 10 years was 8% and 19%, respectively. CONCLUSION: The outcomes for patients completing multimodality therapy compare favorably with published data; however, the exclusion of patients with progression during induction chemotherapy may account in part for these results. The pathologic complete response rate was found to be an important prognostic factor. Selected patients with inflammatory breast cancer have the potential for long-term survival.

Metz JM, Schultz DJ, Fox K, Glick J, Solin LJ. · Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, USA. · Cancer J Sci Am. · Pubmed #10198729 No free full text.

Abstract: PURPOSE: Postmastectomy radiation therapy is often recommended for patients at high risk for local-regional recurrence after mastectomy. However, long-term outcomes after radiation therapy are not well described. PATIENTS AND METHODS: Between 1977 and 1992, 221 patients at high risk for local-regional recurrence of breast cancer after mastectomy were treated with radiation therapy, with or without adjuvant systemic therapy. Patients were classified as high risk because of T3 or T4 tumors (14%), positive lymph nodes (29%), close or positive margins of resection (15%), or multiple risk factors (39%); 4% did not meet current criteria for radiation therapy. The median age of patients was 51 years. Radiation therapy consisted of 45 to 50.4 Gy to the chest wall in 1.8 to 2.0 Gy fractions. The regional lymph nodes were treated in 187 patients (85%). There were 151 patients (68%) who received adjuvant chemotherapy. Patients who received chemotherapy were younger (median age, 48 years vs 64 years) and had more positive lymph nodes (median, 5 vs 1) than patients not receiving chemotherapy. Adjuvant hormonal therapy was utilized in 116 patients (53%). The median follow-up was 4.3 years. RESULTS: The actuarial 10-year local-regional failure rate was 11% (95% CI: 6.5% to 16.7%). The site of first failure was distant metastases in 75 patients (34%), local-regional recurrence in 11 patients (5%), and both sites in three patients (1%); 60% had no evidence of disease at last follow-up. Of the patients who presented with local-regional recurrence as first failure, nine patients (82%) subsequently developed metastatic disease. The median time to local-regional first failure was 1.3 years. The median time to distant metastases after local-regional first failure was 0.3 years. DISCUSSION: Postmastectomy radiation therapy is associated with an 89% rate of local-regional control in this high-risk population. Patients who experience a local-regional recurrence after radiation therapy are at a very high risk for metastatic disease. Radiation therapy after mastectomy is recommended to optimize local-regional control for high-risk breast cancer patients.

Smith K, Wray L, Klein-Cabral M, Schuchter L, Fox K, Glick J, DeMichele A. · Department of Oncology-Hematology, Memorial-Sloan Kettering Cancer Center, USA. · Clin Breast Cancer. · Pubmed #16137438 No free full text.

Abstract: BACKGROUND: Black patients with breast cancer may be at greater risk for chemotherapy-related hematologic toxicity than white patients because of lower baseline blood cell counts. We hypothesize that these baseline differences could lead to excess hematologic toxicity and greater modification of chemotherapy dosing in black patients and that this may contribute to the poorer survival observed in black patients with breast cancer compared with white patients with breast cancer. PATIENTS AND METHODS: We performed a retrospective cohort study of black and white patients with breast cancer treated with adjuvant chemotherapy at an academic medical center over an 18-month period. Clinical chart review and pharmacy records were used to collect data on the following: modification of chemotherapy dose or administration; hematologic toxicity; blood cell counts before, during, and after therapy; occurrence of febrile neutropenia; use of prophylactic antibiotics; and use of granulocyte colony-stimulating factor in order to determine whether ethnicity was an independent predictor of these outcomes. RESULTS: Among 23 black patients and 98 white patients with breast cancer treated with adjuvant chemotherapy, modification of chemotherapy administration occurred in 56 patients (46%). Modification was more common among black patients (65.2% vs. 41.8%; relative risk [RR], 1.56; P = 0.04). Black patients were more likely to receive reduced cumulative doses of adjuvant chemotherapy (RR, 2.49; P = 0.03). CONCLUSION: Our findings suggest that hematologic tolerability of adjuvant chemotherapy is similar in black and white patients. Strategies aimed at improving psychosocial barriers to adjuvant therapy and at reducing surgical complications in black patients may improve overall breast cancer outcomes in this group.

Santiago RJ, Wu L, Harris E, Fox K, Schultz D, Glick J, Solin LJ. · Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #14697443 No free full text.

Abstract: PURPOSE: To determine the 15-year outcomes for women with early stage breast cancer after breast conservation therapy. METHODS AND MATERIALS: Between 1977 and 1990, 937 women with Stage I and II breast carcinoma (55% T1N0, 16% T2N0, 18% T1N1, and 11% T2N1) underwent lumpectomy, axillary lymphadenectomy, and definitive irradiation. The median patient age was 52 years. Of the 937 patients, 375 (40%) received adjuvant chemotherapy and/or hormonal therapy, including 249 (92%) of the 270 women with pathologically positive nodes. The median follow-up was 10.1 years. RESULTS: For the overall group, the 15-year overall survival rate was 71%, and the rate of freedom from distant metastases was 76%. The 15-year local failure rate was 19%. The 15-year contralateral breast cancer rate was 12%. The most common first events were distant failure (13%), local failure (10%), contralateral breast cancer (7%), and second malignant neoplasms (6%). The local failure rate at 10 years for favorable subsets of tumors characterized by mammographic detection, resection with negative margins, treatment with chemotherapy, and treatment with hormones was 8%, 10%, 10%, and 7%, respectively. Local failures were most commonly observed within (true recurrence), or just outside (marginal miss), the primary tumor bed (66%, 85 of 128). The rate of true recurrence or marginal miss at 5, 10, and 15 years was 5%, 10%, and 12%, respectively. CONCLUSION: These high rates of survival and local control confirm that breast conservation therapy yields favorable results in women with early breast cancer into the second decade after treatment.

Metz JM, Schultz DJ, Fox K, Mathews A, Glick J, Solin LJ. · Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia 19104, USA. · Cancer J. · Pubmed #11079172 No free full text.

Abstract: PURPOSE: The success of adjuvant chemotherapy has prolonged the interval between surgery and postmastectomy radiation therapy for high-risk breast cancer patients. The purpose of this study is to determine whether a delay in radiation therapy after mastectomy results in an increased risk of local-regional recurrence of breast cancer. MATERIALS AND METHODS: A retrospective review was performed of the University of Pennsylvania database of 221 patients with high-risk breast cancer treated with postmastectomy radiation therapy between 1977 and 1992. The surgery to postmastectomy radiation therapy time interval was 2 months or less in 82 patients (37%), 2.1 to 6 months in 50 patients (23%), and greater than 6 months in 89 patients (40%). Adjuvant chemotherapy was utilized in 151 patients (68%). The median follow-up was 4.3 years after postmastectomy radiation therapy. RESULTS: Because the three groups showed significant differences for a number of prognostic factors, outcomes are reported in terms of local-regional recurrence only and not survival. The actuarial rate of local-regional recurrence at 8 years was 13% for patients with a surgery to radiation therapy interval of 2 months or less, 4% for those with an interval of 2.1 to 6 months, and 12% for those with an interval of greater than 6 months. A similar analysis performed for 4 months or less versus greater than 4 months between surgery and postmastectomy radiation therapy showed no difference in local-regional recurrence (11% versus 10%, respectively). CONCLUSIONS: A delay in the institution of postmastectomy radiation therapy in favor of the prolongation of chemotherapy for high-risk breast cancer patients does not adversely affect outcome for local-regional recurrence at 8 years.

DeMichele A, Aplenc R, Botbyl J, Colligan T, Wray L, Klein-Cabral M, Foulkes A, Gimotty P, Glick J, Weber B, Stadtmauer E, Rebbeck TR. · Department of Biostatistics and Epidemiology, Abramson Cancer Center, PA, USA. · J Clin Oncol. · Pubmed #16110016 No free full text.

Abstract: PURPOSE: Adjuvant chemotherapy cures only a subset of women with nonmetastatic breast cancer. Genotypes in drug-metabolizing enzymes, including functional polymorphisms in cytochrome P450 (CYP) and glutathione S-transferases (GST), may predict treatment-related outcomes. PATIENTS AND METHODS: We examined CYP3A4*1B, CYP3A5*3, and deletions in GST mu (GSTM1) and theta (GSTT1), as well as a priori-defined combinations of polymorphisms in these genes. Using a cohort of 90 node-positive breast cancer patients who received anthracycline-based adjuvant chemotherapy followed by high-dose multiagent chemotherapy with stem-cell rescue, we estimated the effect of genotype and other known prognostic factors on disease-free survival (DFS) and overall survival (OS). RESULTS: Patients who carried homozygous CYP3A4*1B and CYP3A5*3 variants and did not carry homozygous deletions in both GSTM1 and GSTT1 (denoted low-drug genotype group) had a 4.9-fold poorer DFS (P = .021) and a four-fold poorer OS (P = .031) compared with individuals who did not carry any CYP3A4*1B or CYP3A5*3 variants but had deletions in both GSTT1 and GSTM1 (denoted high-drug genotype group). After adjustment for other significant prognostic factors, the low-drug genotype group retained a significantly poorer DFS (hazard ratio [HR] = 4.9; 95% CI, 1.7 to 14.6; P = .004) and OS (HR = 4.8; 95% CI, 1.8 to 12.9; P = .002) compared with the high- and intermediate-drug combined genotype group. In the multivariate model, having low-drug genotype group status had a greater impact on clinical outcome than estrogen receptor status. CONCLUSION: Combined genotypes at CYP3A4, CYP3A5, GSTM1, and GSTT1 influence the probability of treatment failure after high-dose adjuvant chemotherapy for node-positive breast cancer.