Radiotherapy for early stage favourable breast cancers.
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Breast Neoplasms↗
Biomedical subjects
S E Singletary
Publications and source records attributed to S E Singletary.
Sensitivity to benzo(a)pyrene diol-epoxide associated with risk of breast cancer in young women and modulation by glutathione S-transferase polymorphisms: a case-control study.
Mounting epidemiological evidence suggests that smoking may play a role in the etiology of breast cancer. Because smoking-related DNA adducts are detectable in both normal and malignant breast tissues, we hypothesized that breast cancer patients may be sensitive to tobacco-induced carcinogenesis, and this sensitivity could be modulated by variants of metabolic genes. To test this hypothesis, we evaluated benzo(a)pyrene diol-epoxide (BPDE)-induced mutagen sensitivity and polymorphisms of GSTM1 and GSTT1 in a pilot case-control study of breast cancer. Short-term cell cultures were established from blood samples of 100 female breast cancer patients and 105 healthy controls. After 5 h of in vitro exposure to 4 microM of BPDE, we harvested the lymphocytes for cytogenetic evaluation and recorded and compared the frequency of BPDE-induced chromatid breaks between cases and controls. We used a multiplex PCR-based assay to simultaneously detect polymorphisms of GSTM1 and GSTT1 from genomic DNA. We performed univariate and multivariate logistic regression analyses and calculated odds ratios (OR) and 95% confidence intervals (CIs). Cases had a significantly higher frequency of chromatid breaks than did controls (P < 0.0001). The level of chromatid breaks greater than the median value of controls was associated with a >3-fold increased risk of breast cancer [adjusted odds ratio (ORadj) = 3.11; 95% CI = 1.72-5.64]. The risk was more pronounced in those who were < 45 years (ORadj = 4.79; 95% CI = 1.87-12.3), ever-smokers (ORadj = 5.55; 95% CI = 1.85-16.6), alcohol drinkers (ORadj = 4.64; 95% CI = 1.70-12.7), and those who had the GSTT1 null variant (ORadj = 8.01; 95% CI = 1.16-55.3). These data suggest that sensitivity to BPDE-induced chromosomal aberrations may contribute to the risk of developing breast cancer, and such sensitivity may be modulated by both genetic and environmental factors. Larger studies are needed to confirm our findings.
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
DOC-2/hDab-2 inhibits ILK activity and induces anoikis in breast cancer cells through an Akt-independent pathway.
DOC-2/hDab-2 was identified due to the loss of its expression in primary ovarian cancer cells. It is believed that loss of DOC-2/hDab-2 expression is one of the early events of ovarian malignancy. These results suggest a function of DOC-2/hDab-2 as a tumor suppressor. However, it is not clear how DOC-2/hDab-2 negatively regulates cancer cell growth. In this report, we demonstrate that DOC-2/hDab-2 expression in breast cancer cells resulted in sensitivity to suspension-induced cell death (anoikis). This event was associated with the down-regulation of the integrin-linked kinase (ILK) activity. Since ILK is a key factor in regulating the cellular signaling in responding to the extracellular signals through adhesion molecules like integrins, our results indicate that DOC-2/hDab-2 may prevent tumor growth and invasion by modulating the anti-apoptotic ILK pathway.
Adaptor Proteins, Signal Transducing↗
Breast conservation therapy as a treatment option for the elderly. The M. D. Anderson experience.
BACKGROUND: Although almost half of all incidents of breast carcinoma occur in women age > or = 65 years, not enough is known about appropriate care for patients in this age group. The objective of the current study was to evaluate the role of breast conservation therapy in the management of breast carcinoma in women age > or = 65 years. METHODS: From 1970 to 1994, 1325 patients with carcinoma of the breast were treated with breast conservation therapy (segmental mastectomy and radiation therapy with or without axillary lymph node dissection) at The University of Texas M. D. Anderson Cancer Center. From this patient group, the authors identified 184 elderly women (> or = 65 years) with Stage 0-III disease at the time of diagnosis. RESULTS: The median patient age was 70 years (range, 65-88 years). The distribution of disease by stage among the women was Stage 0 disease in 12 patients (7%), Stage I disease in 107 patients (58%), Stage II disease in 63 patients (34%), and Stage III disease in 2 patients (1%). Comorbid conditions that may have influenced treatment planning were reported in 91 patients (50%). An axillary lymph node dissection was performed in 135 patients (73%), with positive axillary lymph nodes found in 30 patients (22%). Adjuvant chemotherapy was given to 10 patients (5%), and tamoxifen therapy was given to 63 patients (34%). Complications from treatment were reported in 24 patients (13%). With a median follow-up of 7.3 years (range, 0.25-23.5 years), 9 patients developed locoregional disease recurrence (5%), 10 patients developed contralateral breast carcinoma (5%), and 21 patients developed distant metastasis (11%). At last follow-up, 113 patients (61%) were alive, 15 patients (8%) were dead of disease, and 56 patients (30%) were dead of other causes. The 5-year and 10-year disease specific survival rates were 96% and 91%, respectively. CONCLUSIONS: Breast conservation therapy with segmental mastectomy and postoperative radiation therapy with or without axillary lymph node dissection provides excellent local control and disease free survival in elderly women with breast carcinoma. This treatment should be considered as the standard of care for elderly patients without severe comorbid disease.
Aged↗
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.
Adult↗
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.
Adult↗
A case-control study of unilateral and bilateral breast carcinoma patients.
BACKGROUND: Women with unilateral breast carcinoma are at increased risk for developing contralateral disease. The clinical significance of bilateral breast carcinoma has not been fully defined, and the subset of patients who may benefit from medical or surgical risk-reduction intervention has not yet been characterized. The purpose of this study was to evaluate risk factors and outcomes for bilateral breast carcinoma. METHODS: A subject group of 70 bilateral breast carcinoma patients (62% metachronous) was matched by age and survival interval with a control group of 70 unilateral breast carcinoma patients. Median follow-up was 103 months. RESULTS: Eighty-two percent of the unilateral patients and 80% of the bilateral patients had Stage I or II disease at diagnosis. Median age at presentation was 53 years. In the bilateral group, the contralateral cancer was diagnosed at the same or earlier stage than the first cancer in 87% of cases. Bilateral patients were significantly more likely to have multicentric disease and to have a positive family history for breast carcinoma compared with the unilateral group. There were no significant differences regarding history of exogenous hormone exposure, lobular histology, hormone-receptor status, or HER-2/neu expression. Five-year disease-free survival was 94% for the unilateral breast carcinoma patients and 91% for the bilateral breast carcinoma patients (P = 0.16). CONCLUSIONS: Survival for patients with bilateral breast carcinoma is similar to that of patients with unilateral disease; however, prophylactic risk-reduction intervention for the contralateral breast should be considered in patients who have multicentric unilateral disease or a positive family history for breast carcinoma.
Adult↗
Unusual aspects of breast cancer: case 3. Blue hives during lymphatic mapping for breast cancer.
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Aged↗
Impact of systemic treatment on local control for patients with lymph node-negative breast cancer treated with breast-conservation therapy.
PURPOSE: To determine the impact of tamoxifen and chemotherapy on local control for breast cancer patients treated with breast-conservation therapy. PATIENTS AND METHODS: The data from 484 breast cancer patients who were treated with breast-conserving surgery and radiation were analyzed. Only patients with lymph node-negative disease were studied to provide comparative groups with a similar stage of disease and a similar competing risk for distant metastases. Actuarial local control rates of the 277 patients treated with systemic therapy (128, chemotherapy with or without tamoxifen; 149, tamoxifen alone) were compared with the rates for the 207 patients who received no systemic treatment. Only 10% of the patients had positive (2%), close (3%), or unknown margin status (5%). RESULTS: Patients treated with systemic therapy had improved 5-year (97.5% v 89.8%) and 8-year (95.6% v 85.2%) local control rates compared with those that did not receive systemic treatment (P =.004, log-rank test). There was no statistical difference in local control between patients treated with chemotherapy and patients treated with tamoxifen alone (P =.219). Systemic treatment, margin status, young patient age, estrogen and progesterone receptor status, and primary tumor size were analyzed in a Cox regression analysis. The use of systemic treatment was the most powerful predictor of local control: patients who did not receive systemic treatment had a relative risk of local recurrence of 3.3 (95% confidence interval, 1.5 to 7.5; P =.004). CONCLUSION: In this retrospective analysis, systemic therapy appears to contribute to long-term local control in patients with lymph node-negative breast cancer treated with breast-conservation therapy.
Adult↗
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.
Adult↗
Biologic basis and evolving role of aromatase inhibitors in the management of invasive carcinoma of the breast.
BACKGROUND AND OBJECTIVES: The most powerful predictor of the response of breast cancers to hormonal therapy is the presence of estrogen receptors in the tumor cells. Estrogen receptors are expressed in approximately 35-55% of all breast tumors but up to 80-90% of tumors from women older than 55 years. METHODS: At this time, tamoxifen remains the first-line hormonal therapy for breast cancer of all stages. However, the aromatase inhibitors are evolving into an important treatment option. Aromatase inhibitors prevent the conversion of precursors (androgens) to estrogens. RESULTS: On the basis of several randomized clinical trials, aromatase inhibitors have become established as the second-line therapy for postmenopausal women with advanced breast cancer progressing during tamoxifen therapy. Furthermore, very recent trials support the use of these agents as first-line therapy in place of tamoxifen. CONCLUSIONS: The roles of the selective aromatase inhibitors in the prevention of breast cancer and in the neoadjuvant and adjuvant treatment of early-stage breast cancer are the focus of several planned and ongoing large-scale clinical trials. These trials will answer some of the many questions that remain regarding optimal hormonal therapy for hormone-dependent breast cancer.
Antineoplastic Agents, Hormonal↗
Educational review: role of the surgeon in hereditary breast cancer.
Up to 10% of the breast cancers detected in the United States are related to an inherited germline mutation, usually in the BRCA1 or BRCA2 genes, and the majority of these patients will at some point require surgical evaluation and/or treatment. Women who harbor a genetic predisposition for breast cancer face an increased risk for early onset disease, bilateral tumors, and other non-breast malignancies, such as ovarian cancer. These issues raise questions regarding the appropriate surveillance regimen, and the potential efficacy of risk reduction strategies that should be considered. Once a breast cancer diagnosis has been established, the prognosis appears to be similar to stage-controlled sporadic breast cancer, despite an increased prevalence of adverse primary tumor features. However, the role of breast conservation therapy for these patients and the optimal means of addressing the substantially increased risk for contralateral tumors is not yet defined. The reported literature in this area, including a discussion of the value of genetic counseling and genetic testing, is reviewed.
Adult↗
Feasibility of breast preservation in the treatment of occult primary carcinoma presenting with axillary metastases.
BACKGROUND: The objective of the study was to compare the treatment outcomes in patients with occult primary carcinoma with axillary lymph node metastasis who were treated with mastectomy or with intent to preserve the breast. METHODS: From 1951 to 1998, 479 female patients were registered with axillary lymph node metastasis from an unknown primary. After clinical workup, including mammography, 45 patients retained this diagnosis and received treatment for T0 N1-2 M0 carcinoma of the breast. Clinical and pathological data were collected retrospectively, and survival was calculated from the date of initial diagnosis using the Kaplan-Meier method. Median follow-up time was 7 years. RESULTS: Median age was 54 years (range, 32-79). Clinical nodal status was N1 in 71% and N2 in 29% of the patients. Surgical treatment was mastectomy in 29% and an intent to preserve the breast in 71% of the patients. Locoregional radiotherapy was used in 71% and systemic chemoendocrine therapy was used in 73% of the patients. Of the 13 mastectomy patients, only one had a primary tumor discovered in the specimen. Two patients (4%) were ultimately diagnosed with lung cancer and neuroendocrine tumor. No significant difference was detected between mastectomy and breast preservation in locoregional recurrence (15% versus 13%), distant metastases (31% versus 22%), or 5-year survival (75% vs. 79%). Regardless of surgical therapy, the most important determinant of survival was the number of positive nodes. Five-year overall survival was 87% with 1-3 positive nodes compared with 42% with > or =4 positive nodes (P < .0001). CONCLUSIONS: Occult primary carcinoma with axillary metastases can be treated with preservation of the breast without a negative impact on local control or survival.
Adult↗
Utility of breast sentinel lymph node biopsy using day-before-surgery injection of high-dose 99mTc-labeled sulfur colloid.
BACKGROUND: In sentinel lymph node (SLN) biopsy for breast cancer, many centers use same-day preoperative injection of technetium 99mTc-labeled sulfur colloid and intraoperative injection of blue dye for localization of SLNs. Same-day sulfur colloid injections can be problematic because of the variability in sulfur colloid migration times, which can lead to ineffective use of operating room time, and low SLN-to-background radioactivity ratios. We examined the utility of day-before-surgery injections of high dose 99mTc-labeled sulfur colloid injections. METHODS: The day before surgery, high-dose 99mTc-labeled sulfur colloid was injected peritumorally, and a lymphoscintigram was obtained. Intraoperatively, after injection of blue dye, a gamma probe was used to localize SLNs. Nodes that were stained blue or were highly radioactive were considered SLNs and were removed. RESULTS: Lymphoscintigraphy demonstrated drainage in 107 patients (91%). Transcutaneous localization of the SLN was possible in 104 patients (89%). In three patients, all of whom had no drainage demonstrated on lymphoscintigraphy, no SLN was identified at surgery (97.5% success rate for SLN identification). A mean of 2.3 SLNs per patient were identified. Twenty-five patients (21%) had at least one histologically positive SLN. In 23 of these patients, the positive SLN was the SLN with the most radioactivity, and in the remaining two patients, the positive SLN was both blue-stained and hot. CONCLUSION: Day-before-surgery injection of high-dose 99mTc-labeled sulfur colloid results in high rates of transcutaneous and intraoperative identification of SLNs. The delay between injection and surgery did not appear to promote significant passage of sulfur colloid to second-echelon nodes.
Adult↗
Reduction mammoplasty improves breast conservation therapy in patients with macromastia.
BACKGROUND: Macromastia has been considered a contraindication to breast conservation therapy because of difficulties with radiation therapy. This study evaluates the feasibility of bilateral reduction mammoplasty as a component of breast conservation therapy for breast cancer patients with pendulous breasts. METHODS: Of 153 patients undergoing reduction mammoplasty at the University of Texas M. D. Anderson Cancer Center, 28 were identified as breast cancer patients with macromastia receiving breast conservation therapy. Median follow-up was 23.8 months. RESULTS: Median patient age was 55 years. Nearly all patients were described as obese. Median weight of the reduction mammoplasty specimen on the cancerous side was 766 g. One patient (4%) required completion mastectomy for inadequate margin control. Major postoperative complications occurred in 2 patients (7%). There were no major postradiation complications. Patient survey revealed a satisfaction rate of 86%. CONCLUSION: Bilateral reduction mammoplasty is a reasonable and safe option for breast cancer patients with macromastia who desire breast conservation therapy.
Adult↗
Adverse prognostic significance of infraclavicular lymph nodes detected by ultrasonography in patients with locally advanced breast cancer.
BACKGROUND: Ultrasonography is increasingly used to evaluate the nodal status of breast cancer patients and specialized positioning permits assessment of the infraclavicular fossa. However, the incidence and significance of infraclavicular (level III) adenopathy detected sonographically in locally advanced breast cancer (LABC) has not been defined. METHODS: The study population consisted of 146 LABC patients registered in a prospective trial of induction chemotherapy between 1991 and 1996. All patients underwent ultrasound imaging before and after chemotherapy. Median follow-up was 32 months. RESULTS: Forty-two of 146 patients (29%) had suspicious infraclavicular adenopathy; all 42 had additional positive axillary lymph nodes by ultrasound. Disease-free and overall survival for the patients with suspicious infraclavicular adenopathy was significantly worse compared with patients without this feature; disease-free survival 50% versus 68% (P = 0.112); overall survival 58% versus 83% (P = 0.026). CONCLUSIONS: Nearly one third of LABC patients will have infraclavicular lymph node involvement by ultrasound imaging; this finding is a significant adverse prognostic feature, and we recommend that infraclavicular nodal evaluation become a routine component of the sonographic workup of breast cancer patients, particularly if lower axillary lymph nodes appear involved.
Adult↗
Neoadjuvant chemotherapy in the treatment of stage II and III breast cancer.
The current attractiveness of neoadjuvant chemotherapy lies in its ability to downstage both the primary tumor and the axilla, making many patients good candidates for breast-conserving surgical techniques. This has been an important achievement in a patient group whose tumors are often considered inoperable. Attention has more recently turned to the use of neoadjuvant chemotherapy in patients with operable tumors. In patients with resectable stage II and III breast tumors, neoadjuvant chemotherapy has been demonstrated to provide effective downstaging of the primary tumor, and subsequent breast-conserving surgery results in excellent local control. In addition, neoadjuvant chemotherapy has been shown to downstage axillary lymph nodes from positive to negative in a significant number of cases. This raises the question of whether patients who have clinically negative axillae after neoadjuvant chemotherapy need to risk the morbidity associated with axillary lymph node dissection. Axillary irradiation may provide adequate regional control in patients who are clinically node negative. In addition, sentinel lymph node dissection has been shown to provide accurate assessment of the axilla in patients who have received neoadjuvant chemotherapy. An important ramification of the concept of neoadjuvant chemotherapy is that surgery that takes place after the completion of systemic therapy can become minimally invasive, accomplished in an outpatient setting without the need for an operating room suite.
Axilla↗
Image-guided surgery of small breast cancers.
BACKGROUND: Widespread screening mammography has resulted in detection of many breast cancers smaller than one cm. Image-guided percutaneous needle sampling provides accurate diagnostic and prognostic information for adjuvant therapy. Less invasive methods based on imaging techniques are emerging as an alternative to wire localization and lumpectomy. DATA SOURCES: Information presented in this overview was provided by seven investigators from five medical centers in the United States. These researchers are currently developing various techniques of image-guided percutaneous therapy of small (Tis, 1) breast cancers. CONCLUSIONS: Several percutaneous treatment modalities for treatment of early breast cancer, either excisional or in-situ ablative, are described in this overview and their potential applications are discussed.
Biopsy↗