Radiation therapy and patient age in the survival from early-stage breast cancer.

PURPOSE: To analyze the use of radiation therapy following local excision of invasive localized breast cancer and subsequent survival by 5-year age category. METHODS: Data for 27, 399 women diagnosed with localized stage of breast cancer and treated with local excision surgery from 1983 through 1992 were collected and provided by the national Surveillance, Epidemiology, and End Results (SEER) program. Use of radiation therapy was analyzed by race, ethnic background, geographic location, and age at diagnosis. Survival for women treated with local excision plus radiation therapy was compared to that of women treated with local excision alone for each 5-year age category. RESULTS: Subjects in older age groups were significantly less likely (p < 0.001) to receive radiation following local excision compared to younger age groups. Statistically significant survival advantages were conferred on women receiving radiation therapy in each 5-year age category from age 35 to 84 years (ranging from p = 0.02 to p < 0.0001). CONCLUSION: While the use of radiation therapy following local excision of early-stage breast tumors drops significantly in older age groups, women aged 35-84 years receiving radiation therapy had significant reductions in mortality. These results did not appear to be influenced by the presence of mortal comorbid conditions. These results strongly suggest the need to consider carefully patient characteristics other than age in deciding the course of treatment for early-stage breast cancer.     

Effect of pregnancy on overall survival after the diagnosis of early-stage breast cancer.

PURPOSE: To evaluate the impact of subsequent pregnancy on the prognosis of patients with early breast cancer. PATIENTS AND METHODS: One hundred eight patients who became pregnant after diagnosis of early-stage breast cancer were identified in institutions participating in International Breast Cancer Study Group (IBCSG) studies. Fourteen had relapse of breast cancer before their first subsequent pregnancy. The remaining 94 patients (including eight who relapsed during pregnancy) formed the study group reported here. A comparison group of 188 was obtained by randomly selecting two patients, matched for nodal status, tumor size, age, and year of diagnosis from the IBCSG database, who were free of relapse for at least as long as the time between breast cancer diagnosis and completion of pregnancy for each pregnant patient. Survival comparison used Cox proportional hazards regression models. RESULTS: Overall 5- and 10-year survival percentages (+/- SE) measured from the diagnosis of early-stage breast cancer among the 94 study group patients were 92% +/- 3% and 86% +/- 4%, respectively. For the matched comparison group survival was 85% +/- 3% at 5 years and 74% +/- 4% at 10 years (risk ratio, 0.44; 95% confidence interval, 0.21 to 0.96; P =.04). CONCLUSION: Subsequent pregnancy does not adversely affect the prognosis of early-stage breast cancer. The superior survival seen in this and other controlled series may merely reflect a healthy patient selection bias, but is also consistent with an antitumor effect of the pregnancy.     

Conservative therapy for early-stage breast cancer

An evaluation of the data on the treatment of 298 cases of breast cancer (stages IIa and IIb) showed that a reduced frequency of loco-regional recurrences, after post-operative irradiation as a component of conservative therapy, was followed by improvement in quality of life. This was particularly apparent in patients with pT2pN1 tumors. It was also found that after extended dissection of axillary lymph nodes at all three levels, a dose of 50 Gy was sufficient without additional irradiation of the cicatrix. Nor was it necessary to expose the axillary area in cases of three or less lymph node recurrences provided that at least 6 resected nodes were studied histologically. Following conservative therapy, 5-year survival was 97%, while relapse-free survival--82%.     

Breast-conserving therapy for early-stage breast cancer

In most other organs (extremities, bladder, rectum, larynx, or eye), the acceptance of organ-conserving therapy into standard oncologic practice has required only the demonstration of feasibility and efficacy--not equivalency with the radical surgical alternative. BCT was not generally accepted as standard oncologic practice until the maturation of numerous prospective randomized trials that universally demonstrated equivalence in disease control outcomes and survival with mastectomy. In fact, the acceptance of BCT as standard therapy in many parts of the United States actually lagged more than a decade behind sentinel publications documenting proof of equivalency with mastectomy. Even today, investigators continue to search for a subset of breast cancer patients who will have better disease control with radical surgery. BCT stands as not only the best-studied example of organ-conserving therapy but one of the most rigorously tested therapies in all of medicine. Breast-conserving therapy requires a multidisciplinary approach with close coordination among team members from diagnosis through surveillance following treatment. The surgeon must be willing to assess and re-excise margins, to mark the tumor bed with clips, and to use sentinel node biopsy in appropriate patients. The radiation oncologist must be willing to use CT planning, paying close attention not only to coverage of target tissues but to avoidance of critical normal tissues. The medical oncologist must work closely with the surgeon and radiation oncologist to determine the optimal sequencing of therapies and selection of systemic agents. All must recognize special circumstances where genetic counselling may be beneficial, psychosocial support may be needed, or BCT may not be the best choice for patients. When used appropriately, BCT produces maximal disease control and quality of life while minimizing iatrogenic functional, cosmetic, and psychologic sequelae in patients with early-stage breast cancer. BCT serves as a model for the optimal combination of surgery and radiation in organ-preserving cancer therapy.     

Developments in the systemic therapy of early-stage breast cancer

Breast cancer is a heterogeneous disease classified by variations in gene expression, and as such, concepts regarding treatment recommendations according to molecular classification are being explored. Retrospective data from hypothesis-generating subset analyses of adjuvant clinical trials have shown that patients with lower oestrogen receptor (ER) expression are more likely to benefit from adjuvant chemotherapy compared with patients who have intermediate or high ER expression. In addition, greater benefit is obtained from increasing the dose density of chemotherapy for ER-negative versus ER-positive disease, although some ER-positive patients do benefit from more aggressive chemotherapy. A high research priority is to identify those ER-positive patients who will benefit from multi-agent chemotherapy. Subset analyses have also shown that patients with progesterone receptor (PR)-negative disease may benefit from taxane-based chemotherapy, regardless of ER status. Furthermore, adjuvant trastuzumab should be considered in human epidermal growth factor receptor-2-positive patients who have a moderate/high risk of recurrence. These molecular classifications are being used to design clinical trials to enable adjuvant treatment recommendations to be made based not only on prognostic factors but also on predictive factors for benefit. In future, therapies will increasingly target particular molecular subsets and, as a result, become more effective.     

Progress in systemic adjuvant therapy of early-stage breast cancer

Despite major improvements in the treatment of early-stage breast cancer over the past 15 years, many controversies exist surrounding the optimal adjuvant therapies for these patients. Adjuvant chemotherapy has been demonstrated to reduce recurrence and improve mortality, but questions persist as to what is the optimal regimen and how much adjuvant therapy should be administered. Among the adjuvant chemotherapy issues that remain controversial are the role of the taxanes and the optimal number of adjuvant chemotherapy treatment cycles. In the realm of adjuvant endocrine therapy, the early results of the Anastrozole, Tamoxifen and Combination (ATAC) trial have led to confusion as to how best to treat postmenopausal patients with estrogen receptor-positive, early-stage breast cancer. Clinicians are faced with the decision of choosing between tamoxifen and anastrozole. The enthusiasm for so-called targeted therapies, such as trastuzumab, in patients with metastatic disease, is now being carried over into the adjuvant setting. Multiple clinical trials around the world are evaluating the potential benefit of adding trastuzumab to chemotherapy in patients with HER2-positive, early-stage breast cancer. In the United States, clinicians are faced with many decisions on how to optimally treat patients with early-stage breast cancer. Evidence-based treatment guidelines such as those developed by the National Comprehensive Cancer Network (NCCN) provide a useful algorithm for assisting in making treatment decisions. It is hoped that, in the next few years, the results of ongoing clinical trials now underway will lead to further improvements in the outcome of patients with early-stage breast cancer.Presentation made at the ASCO-JSCO Joint Symposium held at Tokyo, Japan, on October 18, 2002.     

Role of adjuvant endocrine therapy in early-stage breast cancer

The value of adjuvant endocrine therapy in saving lives of women with estrogen receptor-positive (ER(+)) early-stage breast cancer cannot be disputed. Tamoxifen has proven to be effective in improving relapse-free and overall survival in both pre- and postmenopausal women with ER(+) early-stage breast cancer. In the meta-analysis of the Early Breast Cancer Trialists' Collaborative Group, the proportional reduction in recurrence and mortality for 5 years of tamoxifen therapy was 50% and 28% respectively for patients with ER(+) tumors. These reductions in recurrence and mortality were similar in both lymph node-negative (N(-)) and lymph node-positive (N(+)) patients and translate to an absolute improvement in 10-year survival of approximately 11% in N(+) patients and 6% in N(-) patients. Current data suggest that about 5 years of tamoxifen therapy is the optimal duration of treatment. For women with ER(-)/progesterone receptor-negative (PR(-)) tumors, tamoxifen does not lower the risk of distant metastases or improve survival. In ER(+) patients, the addition of tamoxifen to chemotherapy further lowers the risk of recurrence by about 30% to 40% when compared to chemotherapy alone. In premenopausal women with ER(+) breast cancer, ovarian ablation has proven to be as effective as chemotherapy in improving both relapse-free and overall survival and the potential additive role of ovarian ablation to chemotherapy and/or tamoxifen is presently being explored in clinical trials. The combination of tamoxifen and ovarian ablation is currently being tested and may be superior to tamoxifen alone. In addition, newer, more effective, and less toxic aromatase inhibitors are also being evaluated in clinical trials in the adjuvant setting and have great promise. "Pure" antiestrogens or selective estrogen receptor down-regulators (SERDs) will be studied in adjuvant clinical trials in the near future. Recent data also suggest that molecular markers such as HER-2/neu may predict the response to endocrine therapy, and other predictive factors are currently being evaluated. Lastly, there is renewed interest in neoadjuvant endocrine therapy, a treatment option that may select those patients with early-stage breast cancer most likely to benefit from endocrine therapy.     

Racial disparities in treatment and survival among women with early-stage breast cancer.

PURPOSE: Black women with breast cancer are known to have poorer survival than white women. Suboptimal treatment may compromise the survival benefits of adjuvant chemotherapy. We analyzed the association of race and survival with duration of treatment and number of treatment cycles among women receiving chemotherapy for early-stage breast cancer. PATIENTS AND METHODS: Patients were women in the Henry Ford Health System tumor registry who were diagnosed with stage I/II breast cancer between January 1, 1996, and December 31, 2001, who received adjuvant chemotherapy. We calculated an observed/expected ratio of treatment duration and of completed chemotherapy cycles for each patient. Using Cox proportional hazards models, we analyzed the association of early treatment termination and treatment duration with all-cause mortality, controlling for age, race, stage, hormone receptor status, grade, comorbidity score, and doxorubicin use. RESULTS: Of 472 eligible patients, 28% (31% black, 23% white; P = .03) received fewer cycles of treatment than expected. Black race, receipt of < or = 75% of the expected number of cycles, increasing age, hormone receptor negativity, and a comorbidity score of more than 1 were associated with poorer survival. Among the 344 patients receiving the expected number of cycles, 60% experienced delays. These delays did not reduce survival. CONCLUSION: This study is the first to find that a substantial fraction of women with early-stage breast cancer terminated their chemotherapy prematurely and that early termination was associated with both black race and poorer survival. A better understanding of the determinants of suboptimal treatment may lead to interventions that can reduce racial disparities and improve breast cancer outcomes for all women.     

早期乳腺癌保守性手术后放射治疗进展

保守性手术已成为早期乳腺的主要治疗方式,而放射治疗是乳腺癌保乳综合治疗中一个不可缺少的组成部分,是防止局部复发的根本保证。因此,术后放射治疗很关键。     

BAG-1: a novel biomarker predicting long-term survival in early-stage breast cancer.

PURPOSE: Among women with early-stage breast cancer treated with lumpectomy and radiation therapy, 30% to 40% will develop metastatic disease, which is often fatal. A need exists therefore for biomarkers that distinguish patients at high risk of relapse. We performed a retrospective correlative analysis of BAG-1 protein expression in breast tumors derived from a cohort of early-stage breast cancer patients. PATIENTS AND METHODS: Archival paraffin blocks from 122 women with stages I to II breast cancer treated with lumpectomy and radiation therapy (median follow-up, 12.1 years) were analyzed by immunohistochemical methods using monoclonal antibodies recognizing BAG-1 and other biomarkers, including Bcl-2, estrogen receptor, progesterone receptor, p53, and HER2/Neu. Immunostaining data were correlated with distant metastasis-free survival (DMFS) and overall survival (OS). RESULTS: Cytosolic immunostaining for BAG-1 was upregulated in 79 (65%) of 122 invasive breast cancers (P <.001) compared with normal breast. Elevated BAG-1 was significantly associated with longer DMFS and OS, overall (stages 1 and II) and in node-negative (stage I only) patients, on the basis of univariate and multivariate analyses (DMFS, P =.005; OS, P =.01, in multivariate analysis of all patients; DMFS, P =.005; OS, P =.001, in multivariate analysis of node-negative patients). All other biomarkers failed to reach statistical significance in multivariate analysis. Clinical stage was an independent predictor of OS (P =.04) and DMFS (P =.02). CONCLUSION: These findings provide preliminary evidence that BAG-1 represents a potential marker of improved survival in early-stage breast cancer patients, independent of the status of axillary lymph nodes.     

Recurrence in the breast following conservative surgery and radiation therapy for early-stage breast cancer.

This report summarizes the experience of the Joint Center for Radiation Therapy (JCRT) in treating patients with clinical stage I and II breast cancer with conservative surgery and radiation therapy. The study population consisted of 1396 patients treated between 1968 and 1985. All patients underwent a gross excision of the tumor and received breast irradiation (with or without nodal irradiation) including a "boost" to bring the primary tumor site to a total dose of at least 60 Gy. The method of treatment evolved over the study-time period. During the interval from 1968 to 1982, patients typically underwent a limited gross excision of the tumor without regard to the microscopic margins of resection. During the period 1983 to 1985, film-screen mammography, inking of specimen margins, and reexcisions for inevaluable or involved margins were more commonly performed. With a median follow-up of 80 months, the 5-year crude rate of failure in the breast (as the first site of failure) was 8% (106/1396) and the crude rate of regional nodal/distant failure (as the first site of failure) was 16% (228/1396). The time-course of failures in the breast was protracted, occurring at a fairly constant rate over the first 7 years after treatment, but still seen beyond that point. Most recurrences in the breast (75%) developed at or near the original tumor site. The most important risk factor for developing a breast recurrence was the presence of an extensive intraductal component in the tumor. The cosmetic results following treatment were excellent or good in the majority of patients (87%) and were most adversely affected by extensive surgery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Biopsy findings after breast conservation therapy for early-stage invasive breast cancer

PURPOSE: To determine the patterns and factors predictive of positive ipsilateral breast biopsy after conservation therapy for early-stage breast cancer. METHODS AND MATERIALS: We performed a retrospective review of Stage I-II breast cancer patients initially treated with lumpectomy and radiotherapy between 1977 and 1996, who later underwent post-treatment ipsilateral breast biopsies. RESULTS: A total of 223 biopsies were performed in 193 treated breasts: 171 single and 22 multiple biopsies. Of the 223 biopsies, 56% were positive and 44% were negative for recurrence. The positive biopsy rate (PBR) was 59% for the first and 32% for subsequent biopsies. The median time to the first post-treatment biopsy was 49 months. Of the patients with negative initial biopsy findings, 11% later developed local recurrence. The PBR was 40% among patients with physical examination findings only, 65% with mammographic abnormalities only, and 79% with both findings (p = 0.001). Analysis of the procedure type revealed a PBR of 86% for core and 58% for excisional biopsies compared with 28% for aspiration cytology alone (p = 0.025). The PBR varied inversely with age at the original diagnosis: 49% if >or=51 years, 57% if 36-50 years, and 83% if 180 months after completing postlumpectomy radiotherapy (p = 0.01). The PBR was not linked with recurrence location, initial pathologic T or N stage, estrogen receptor/progesterone receptor status, or final pathologic margins (all p >or= 0.15). CONCLUSION: After definitive radiotherapy for early-stage breast cancer, a greater PBR was associated with the presence of both mammographic and clinical abnormalities, excisional or core biopsies, younger age at the initial diagnosis, and longer intervals after radiotherapy completion.     

Breast-conserving therapy (BCT) for early-stage breast cancer

Several patient and tumor factors go into the decision process to determine whether a breast cancer patient is a good candidate for breast-conserving therapy. The patient must be seen by all disciplines before any therapeutic intervention. When used appropriately, breast-conserving therapy produces maximal disease control and improves quality of life in patients with early-stage breast cancer.     

Impact of patient distance to radiation therapy on mastectomy use in early-stage breast cancer patients.

PURPOSE: Treatment access underlies quality cancer care. We hypothesize that mastectomy rates in a rural state are independently influenced by distance to radiation therapy (XRT) and by changing XRT access through opening new facilities. PATIENTS AND METHODS: Early-stage breast cancer patients diagnosed from 1996 to 2000 were identified in the Virginia state registry. Distance from patient zip code to nearest XRT facility was calculated with geographical software. Distance to XRT facility (< or = 10, > 10 to 25, > 25 to 50, and > 50 miles), American Joint Committee on Cancer tumor stage, age, race, and diagnosis year were evaluated for influencing mastectomy rate. Mastectomy use within 15 miles of five new facilities was assessed before and after opening. RESULTS: Among 20,094 patients, 43% underwent mastectomy, 53% underwent lumpectomy, and therapy of 4% of patients is unknown. Twenty-nine percent of patients lived more than 10 miles from XRT facility. Mastectomy increased with distance to XRT facility (43% at < or = 10 miles, 47% at > 10 to 25 miles, 53% at > 25 to 50 miles, and 58% at > 50 miles; P < .001). Among 11,597 patients with T1 (< 2 cm) tumors, mastectomy also varied by distance (31% at < or = 10 miles, 36% at > 10 to 25 miles, 41% at > 25 to 50 miles, and 49% at > 50 miles; P < .001). In multivariate analysis, mastectomy use was independently influenced by XRT distance after adjusting for age, race, T stage, and diagnosis year. Over the study period, mastectomy rates declined from 48% to 43% across Virginia, and there were similar declines in a 15-mile area around four new radiation facilities in urban settings. However, mastectomies decreased from 61% to 45% around a new XRT facility in a rural setting. CONCLUSION: Distance to XRT facility significantly impacts mastectomy use. Opportunities for increasing breast-conservation rates through improved XRT access exist.     

Selection of optimal adjuvant endocrine therapy for early-stage breast cancer

Opinion statement Oophorectomy was found to cause regression of advanced breast cancer toward the end of the 19th century. Decades later, the discovery that estrogen plays a central role in this process eventually led to two important consequences: first, different modalities were developed to suppress or antagonize estrogen; and second, the ability to detect estrogen receptor in breast cancer tissue became a predictor of response to treatment—probably the best marker for response among all solid tumors. Tamoxifen, which works by competitively antagonizing hormonal receptors in breast cancer cells, has been for the past three decades the standard of care for adjuvant therapy for any woman with hormone receptor-positive early breast cancer, regardless of nodal status or menopausal setting. But as we strive to improve the utility of antagonizing or suppressing estrogen, new modalities are being developed. In the premenopausal setting, the advent of gonadotropin hormone-releasing hormone (also known as luteinizing hormone-releasing hormone) analogues has allowed for medical and reversible suppression of ovarian function. This method has already been proven as effective as chemotherapy in preventing recurrence, and ongoing trials are aiming to better define its role in the adjuvant setting. In the postmenopausal setting, aromatase inhibitors (AIs) have revolutionized the adjuvant treatment of hormone-responsive cancers of all stages. The current standard of care has come to include AIs, as an alternative, in sequence, of after 5 years of tamoxifen. Ongoing research continues to develop agents to overcome hormonal therapy resistance.     

Preoperative breast MRI in early-stage breast cancer

Rapid uptake of new imaging technology is a major contributor to rising healthcare costs. Preoperative breast magnetic resonance imaging (MRI) for patients with early-stage breast cancer has dramatically increased in use without the evidence of improved outcomes compared to standard assessment and is associated with higher rates of mastectomy. A decision analytic model was developed to evaluate the impact of adding breast MRI to the preoperative evaluation of women with early-stage breast cancer who were candidates for breast-conserving therapy on patient outcomes measured in quality-adjusted life years (QALYs). Model inputs, including survival, recurrence rates, and health utilities, were obtained from a comprehensive literature review. One-way sensitivity analyses were performed to estimate threshold values for key parameters at which adding MRI would become the optimal imaging strategy over standard assessment. Preoperative MRI resulted in 17.77 QALYs compared to 17.86 QALYs with standard assessment, a decrease of 0.09 QALYs or 34?days. In sensitivity analyses, standard assessment was associated with better patient outcomes than preoperative breast MRI across all plausible probabilities for mastectomy, local recurrence, and health utilities. For routine preoperative breast MRI to become the optimal strategy, the conversion rate to mastectomy after preoperative MRI would need to be <1?% (versus the range of 3.6-33?% reported in the literature). Routine preoperative breast MRI appears to confer no advantage over the standard diagnostic evaluations for early-stage breast cancer and may lead to worse patient outcomes.