Neoadjuvant chemotherapy for operable breast carcinoma larger than 3 cm: a unicentre randomized trial with a 124-month median follow-up. Institut Bergonie Bordeaux Groupe Sein (IBBGS).
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BACKGROUND: Neoadjuvant chemotherapy improves overall survival and renders possible breast-conserving treatment in locally advanced breast cancer. It was necessary for this method to be evaluated in operable breast tumors too large to be treated immediately by conserving surgery. Initial results of this randomized trial were published in Annals of Oncology (1991). PATIENTS AND METHODS: Women with T2 > 3 cm or T3 N0-1 M0 breast tumors were treated by either initial mastectomy followed by adjuvant chemotherapy, or neoadjuvant chemotherapy followed by adjusted locoregional treatment. Chemotherapy was the same in the two arms. The prognostic and predictive factors of response to chemotherapy were analyzed. RESULTS: Conserving treatments were performed in 63% at the end of neoadjuvant chemotherapy and this rate had decreased to 45% at the median follow-up of 124 months. Survivals are identical in the two treatment groups. Initial clinical tumor size < 40 mm, IHC-ER < 10% and Mib1 > 40% are predictive of tumor response to chemotherapy by uni- and multivariate analyses. For outcome prediction, c-erb-B2 > 0% is the independent prognostic factor for overall and metastasis-free survivals. CONCLUSION: Breast-conserving therapy can be performed in more than half of all cases without alteration of survival, despite a non-negligible rate of local recurrences. (+info)
The influence of margin width on local control of ductal carcinoma in situ of the breast.
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BACKGROUND: Ductal carcinoma in situ is a non-invasive carcinoma that is unlikely to recur if completely excised. Margin width, the distance between the boundary of the lesion and the edge of the excised specimen, may be an important determinant of local recurrence. METHODS: Margin widths, determined by direct measurement or ocular micrometry, and standardized evaluation of the tumor for nuclear grade, comedonecrosis, and size were performed on 469 specimens of ductal carcinoma in situ from patients who had been treated with breast-conserving surgery with or without postoperative radiation therapy, according to the choice of the patient or her physician. We analyzed the results in relation to margin width and whether the patient received postoperative radiation therapy. RESULTS: The mean (+/-SE) estimated probability of recurrence at eight years was 0.04+/-0.02 among 133 patients whose excised lesions had margin widths of 10 mm or more in every direction. Among these patients there was no benefit from postoperative radiation therapy. There was also no statistically significant benefit from postoperative radiation therapy among patients with margin widths of 1 to <10 mm. In contrast, there was a statistically significant benefit from radiation among patients in whom margin widths were less than 1 mm. CONCLUSIONS: Postoperative radiation therapy did not lower the recurrence rate among patients with ductal carcinoma in situ that was excised with margins of 10 mm or more. Patients in whom the margin width is less than 1 mm can benefit from postoperative radiation therapy. (+info)
Breast-conserving therapy: proteases as risk factors in relation to survival after local relapse.
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PURPOSE: To evaluate whether cathepsin D, urokinase-type plasminogen activator (uPA), its inhibitor, plasminogen activator inhibitor-1 (PAI-1), or clinical factors can predict which patients are at risk for developing distant metastases after local recurrence (LR). PATIENTS AND METHODS: Of 1,630 patients treated with breast-conserving surgery and radiotherapy of the breast between 1980 and 1992, LR developed in 171 as a first event. From the available primary tumor tissues, we determined the cytosolic levels of cathepsin D, uPA and PAI-1. RESULTS: In patients with LR, a short (< or = 2 years) disease-free interval (DFI) and skin involvement of LR were associated with poor postrelapse distant metastasis-free survival (PR-DMFS, P = .001, both) and postrelapse overall survival (PR-OS; P < .0001 and P < .0002, respectively). The primary tumor levels of uPA and PAI-1 were elevated for patients with a short DFI (P < .01), but such a relation was not observed for patients with skin involvement. In univariate analyses, high levels of uPA and PAI-1 in the primary tumor were associated with poor PR-OS (P = .038 and P = .040, respectively) but not PR-DMFS. In Cox multivariate analyses for PR-DMFS and PR-OS, only a short DFI and skin involvement of the LR were independently associated with a poor clinical outcome. CONCLUSION: In patients treated with breast-conserving therapy who had LR as a first event, a short DFI and skin involvement were strong indicators for poor PR-DMFS and PR-OS. The proteases studied did not contribute significantly to the final multivariate model. (+info)
Local failure is responsible for the decrease in survival for patients with breast cancer treated with conservative surgery and postoperative radiotherapy.
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PURPOSE: The aim of the present study was to evaluate the role of local failure (LF) in the survival of patients treated with lumpectomy and postoperative radiotherapy and to investigate whether LF is not only a marker for distant metastasis (DM) but also a cause. METHODS: Charts of patients treated with breast conservative surgery between 1969 and 1991 were reviewed retrospectively. There were 2,030 patients available for analysis. The median duration of follow-up was 6 years. A Cox regression multivariate analysis was performed using LF as a time-dependent covariate. RESULTS: Local control (LC) was 87% at 10 years. Local failure led to poorer survival at 10 years than local control (55% v 75%, P < .00). In a Cox model, local failure was a powerful predictor of mortality. The relative risk associated with LF was 3.6 for mortality and 5.1 for DM (P < .00). In patients with LF, the rate of DM peaked at 5 to 6 years, whereas it peaked at 2 years for patients with LC. The mean time between surgery and DM was 1,050 days for patients without LF and 1,650 days for patients with LF (P < .00). CONCLUSION: Our results show that local failure is associated with an increase in mortality. The difference in the time distribution of distant metastasis for LF and LC could imply distinct mechanisms of dissemination. Local failure should be considered not only as a marker of occult circulating distant metastases but also as a source for new distant metastases and subsequent mortality. (+info)
Breast cancer treatment and chemoprevention.
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OBJECTIVE: To outline modern principles of surgery, radiation therapy, and systemic treatment of breast cancer, and to review preliminary data on breast cancer prevention. QUALITY OF EVIDENCE: A MEDLINE search was conducted from 1966 to the beginning of 1999; most of the studies reviewed are randomized clinical trials. MAIN MESSAGE: Breast conservation surgery should be offered to all women with early breast cancer because studies demonstrate survival rates equivalent to those with mastectomy. If mastectomy is chosen, breast reconstruction should be offered. Most women with breast cancer are treated systemically with either chemotherapy or tamoxifen, or both, and mortality is substantially reduced. Data indicating that tamoxifen prevents breast cancer are promising; more studies with both tamoxifen and raloxifene are under way. All women should be strongly encouraged to enter clinical trials. CONCLUSIONS: Because many issues face women recently diagnosed with breast cancer, they often seek out family physicians as advisors to help negotiate a complex treatment path. The possibility of preventing breast cancer will undoubtedly raise questions among family members of women with breast cancer that should appropriately be answered and referred, if necessary, by family physicians. (+info)
Prognosis in women with a carcinoma in situ of the breast: a population-based study in Sweden.
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We studied the risk of invasive breast cancer and breast cancer death after a breast carcinoma in situ during a period when mammography screening became a nationwide practice and when breast conservation was introduced. In a study base including all 4661 women registered to the Swedish Cancer Registry for a first carcinoma in situ between 1960 and 1992, we selected a cohort of 3398 women diagnosed between 1980 and 1992. The recruitment period was chosen according to the reporting routines for the registry. The corrected survival was 97.4% after 10 years. The risk of invasive cancer was similar in the ipsilateral and contralateral breast. Women diagnosed between 1989 and 1992 ran a relative risk of 0.1 (95% confidence interval, 0.0-0.9) of dying of breast cancer, as compared with women diagnosed from 1980-1982. Residence in counties where mammography screening was available was associated with a relative risk of 0.2 (95% confidence interval, 0.0-2.1) for breast cancer death in the age groups screened. Screening mammography may have contributed to the improvement of prognosis over this time period. This study cannot distinguish between lead time effects and a "true" improvement in prognosis. The increased use of breast conservation was not associated with a worse prognosis in the group as a whole. The study indicates that at least 50% of invasive cancers occurring after treatment for in situ lesions may be new cancers. (+info)
BRCA1/BRCA2 germline mutations in locally recurrent breast cancer patients after lumpectomy and radiation therapy: implications for breast-conserving management in patients with BRCA1/BRCA2 mutations.
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PURPOSE: Breast cancer patients treated conservatively with lumpectomy and radiation therapy (LRT) have an estimated lifetime risk of local relapse (ipsilateral breast tumor recurrence [IBTR]) of 10% to 15%. For breast cancer patients carrying BRCA1 or BRCA2 (BRCA1/2) mutations, the outcome of treatment with LRT with respect to IBTR has not been determined. In this study, we estimate the frequency of BRCA1/2 mutations in a study of breast cancer patients with IBTR treated with LRT. PATIENTS AND METHODS: Between 1973 and 1994, there were 52 breast cancer patients treated with LRT who developed an IBTR within the prior irradiated breast and who were willing to participate in the current study. From our database, we also identified 52 control breast cancer patients treated with LRT without IBTR. The control patients were individually matched to the index cases with respect to multiple clinical and pathologic parameters. Lymphocyte DNA specimens from all 52 locally recurrent patients and 15 of the matched control patients under age 40 were used as templates for polymerase chain reaction amplification and dye-primer sequencing of exons 2 to 24 of BRCA1, exons 2 to 27 of BRCA2, and flanking intron sequences. RESULTS: After LRT, eight (15%) of 52 breast cancer patients had IBTR with deleterious BRCA1/2 mutations. By age, there were six (40%) of 15 patients with IBTR under age 40 with BRCA1/2 mutations, one (9.0%) of 11 between ages 40 and 49, and one (3.8%) of 26 older than age 49. In comparison to the six (40%) of 15 of patients under age 40 with IBTR found to have BRCA1/2 mutations, only one (6.6%) of 15 matched control patients without IBTR and had a BRCA1/2 mutation (P =.03). The median time to IBTR for patients with BRCA1/2 mutations was 7.8 years compared with 4.7 years for patients without BRCA1/2 mutations (P =.03). By clinical and histologic criteria, these relapses represented second primary tumors developing in the conservatively treated breast. All patients with BRCA1/2 mutations and IBTR underwent successful surgical salvage mastectomy at the time of IBTR and remain alive without evidence of local or systemic progression of disease. CONCLUSION: In this study, we found an elevated frequency of deleterious BRCA1/2 mutations in breast cancer patients treated with LRT who developed late IBTR. The relatively long time to IBTR, as well as the histologic and clinical criteria, suggests that these recurrent cancers actually represent new primary breast cancers. Early onset breast cancer patients experiencing IBTR have a disproportionately high frequency of deleterious BRCA1/2 mutations. This information may be helpful in guiding management in BRCA1 or BRCA2 patients considering breast-conserving therapy. (+info)
Pathologic and technical considerations in the treatment of ductal carcinoma in situ of the breast with lumpectomy and radiation therapy.
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BACKGROUND: Lumpectomy and radiation therapy is considered a standard treatment option for ductal carcinoma in situ (DCIS) of the breast. The incidence of locally recurrent carcinoma using this therapeutic approach ranges from 6%-19%. Multiple studies have attempted to identify factors associated with the development of local recurrences in these patients. Despite extensive reports examining this issue, no factor(s) has consistently been correlated with outcome. METHODS: This review examines the criteria that various authors have proposed as being associated with recurrence, including DCIS grade, size, histologic subtype, status of surgical margins, and technical factors to help clarify their roles in optimizing treatment outcome. The issue of the definition of the type of recurrence is also addressed. RESULTS: Though multiple studies have examined the impact of grade, histologic subtype, necrosis, and DCIS size on outcome, no consistent results have been observed to suggest that these factors can be routinely used to guide therapy. The adequacy of excision appears to correlate with local control but is imprecisely defined by margin status alone. Based upon recent data, it appears that atypical ductal hyperplasia and cancerization of lobules in the context of coexistent DCIS, may need to be considered as part of the DCIS lesion that should be excised. This issue may account for some of the disparate results of different studies of DCIS. For statistical purposes, recent studies also suggest that only recurrences developing within or adjacent to the bed of the initial DCIS lesion should be considered when analyzing factors associated with outcome. Recurrences developing elsewhere in the breast may include new DCIS and invasive lesions that bear no biologic relationship with the initial DCIS lesion. Finally, since it is impossible to insure that all DCIS has been removed, it may be more appropriate to consider DCIS lesions as adequately or inadequately excised instead of completely or incompletely excised. Since DCIS is essentially a microscopic disease, pathologists should have a primary role in helping to define the adequacy of excision. CONCLUSIONS: Additional studies with complete pathology review and longer follow-up are needed to reach a consensus on which prognostic factors are consistently associated with recurrence for patients with DCIS treated with lumpectomy and radiation therapy. At the present time, adequacy of excision appears to correlate with outcome. However, more precise and consistent methods need to be developed to assist in the determination of adequate DCIS extirpation. (+info)