Preoperative chemotherapy and breast-conserving therapy: why not everyone?
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
A Recht
Publications and source records attributed to A Recht.
Pathologic margin involvement and the risk of recurrence in patients treated with breast-conserving therapy.
BACKGROUND: The relationship between the microscopic margins of resection and ipsilateral breast recurrence (IBR) after breast-conserving therapy for carcinomas with or without an extensive intraductal component (EIC) has not been adequately defined. METHODS: Of 1,790 women with unilateral clinical Stage I or II breast carcinoma treated with radiation therapy as part of breast-conserving therapy, 343 had invasive ductal histology evaluable for an extensive intraductal component (EIC), had inked margins that were evaluable for an review of their pathology slides, and received > or = 60 Gray to the tumor bed; these 343 women constitute the study population. The median follow-up was 109 months. All available slides were reviewed by one of the study pathologists. Final inked margins of excision were classified as negative > 1 mm (no invasive or in situ ductal carcinoma within 1 mm of the inked margin); negative-1 mm, or close carcinoma < or = 1 mm from the inked margin but not at the margin); or positive (carcinoma at the inked margin). A focally positive margin was defined as invasive or in situ ductal carcinoma at the margin in three or fewer low-power fields. The first site of recurrent disease was classified as either ipsilateral breast recurrence (IBR) or distant metastasis/regional lymph node failure. RESULTS: Crude rates for the first site of recurrence were calculated first for all 340 patients evaluable at 5 years, then separately for the 272 patients with EIC-negative cancers and the 68 patients with EIC-positive cancers. The 5-year rate of IBR for all patients with negative margins was 2%; and for all patients with positive margins, the rate was 16%. Among patients with negative margins, the 5-year rate of IBR was 2% for all patients with close margins (negative < or = 1 mm) and 3% for those with negative > 1 mm margins. For patients with close margins, the rates were 2% and 0% for EIC-negative and EIC-positive tumors, respectively; the corresponding rates for patients with negative margins > 1 mm were 1% and 14%. The 5-year rate of IBR for patients with focally positive margins was 9% (9% for EIC-negative and 7% for EIC-positive patients). The 5-year crude rate of IBR for patients with greater than focally positive margins was 28% (19% for EIC-negative and 42% for EIC-positive patients). CONCLUSIONS: Patients with negative margins of excision have a low rate of recurrence in the treated breast, whether the margin is > 1 mm or < or = 1 mm and whether the carcinoma is EIC-negative or EIC-positive. Among patients with positive margins, those with focally positive margins have a considerably lower risk of local recurrence than those with more than focally positive margins, and could be considered for breast-conserving therapy.
Breast Neoplasms↗
Relationship of tumor grade to other pathologic features and to treatment outcome of patients with early stage breast carcinoma treated with breast-conserving therapy.
BACKGROUND: Although histologic grade has previously been described as a predictor of distant failure, it is uncertain whether histologic grade should be used to decide which patients should undergo axillary lymph node dissection and whether grade should be considered as a selection factor for breast-conserving therapy. METHODS: The authors retrospectively analyzed data from 1081 patients with American Joint Committee on Cancer Stage I or II infiltrating ductal carcinoma treated with breast-conserving therapy at the Joint Center for Radiation Therapy between 1970 and 1986. All patients had pathology slides reviewed by one of two study pathologists. Using the Elston modification of the Bloom-Richardson grading system, patients were divided by histologic grade into 3 groups (219 with Grade I, 482 with Grade II, and 380 with Grade III). The median follow-up time for 716 survivors was 134 months. The incidence of various pathologic features was examined with respect to histologic grade. In addition, the 10-year crude rates of failure (by first site) were examined as they related to grade. A polychotomous logistic regression model was used to determine the effect of grade on local and distant failure. RESULTS: High grade tumors tended to be larger, to exhibit more mononuclear cellular reaction and necrosis, and were more likely to be estrogen receptor negative. Patients with high grade tumors were also younger than those with lower grade tumors. The incidence of an extensive intraductal component and lymphatic vessel invasion did not vary significantly by histologic grade. The incidence of pathologic lymph node metastases also did not vary by grade, even when stratified by tumor size. In both univariable and multivariable analyses, the 10-year crude rate of local recurrence was not related to histologic grade (P = 0.44). Distant recurrence rates, however, were significantly higher as grade increased (p = 0.002). CONCLUSIONS: Higher histologic grade predicted an increased incidence of distant recurrence, but not a greater likelihood of axillary lymph node metastases or local recurrence after breast-conserving therapy. The authors conclude that grade should not be used to make decisions regarding local management.
Breast Neoplasms↗
The sequencing of chemotherapy and radiation therapy after conservative surgery for early-stage breast cancer.
BACKGROUND: Patients with early-stage breast cancer who are at substantial risk for systemic metastases are increasingly treated with breast-conserving therapy and adjuvant chemotherapy. However, the optimal sequencing of chemotherapy and radiation therapy is not clear. METHODS: Two hundred forty-four patients with stage I or II breast cancer who were at substantial risk for distant metastases were randomly assigned to receive a 12-week course of chemotherapy either before or after radiation therapy. All had had breast-conserving surgery. The median length of follow-up in surviving patients was 58 months (range, 10 to 124). RESULTS: The five-year actuarial rates of cancer recurrence at any site and of distant metastases in the radiotherapy-first group and the chemotherapy-first group were 38 percent and 31 percent (P = 0.17) and 36 percent and 25 percent (P = 0.05), respectively. Overall survival was 73 percent and 81 percent (P = 0.11), respectively. The five-year crude rates of first recurrence according to site in the radiotherapy-first and chemotherapy-first groups, respectively, were 5 percent and 14 percent for local recurrence and 32 percent and 20 percent for distant or regional recurrence or both. This difference in the pattern of recurrence was of borderline statistical significance (P = 0.07). CONCLUSIONS: This study suggests that for patients ar substantial risk for systemic metastases, it is preferable to give a 12-week course of chemotherapy followed by radiation therapy, rather than radiation therapy followed by chemotherapy.
Actuarial Analysis↗
Radiotherapy and surgery in early breast cancer.
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Breast Neoplasms↗
A prospective study of conservative surgery alone in the treatment of selected patients with stage I breast cancer.
BACKGROUND: Randomized clinical trials have clearly demonstrated that the use of radiation therapy (RT) following breast-conserving surgery (CS) substantially reduces the risk of local recurrence. However, the low rate of local recurrence after CS and RT for patients without known risk factors, and the recent increase in the detection of smaller cancers due to mammographic screening have led to the speculation that a subgroup of patients who have a low risk of local recurrence without RT might be identified. In 1986, we initiated a one-arm, prospective clinical trial of CS alone for treatment of highly selected breast cancer patients without known risk factors for local recurrence. METHODS: The study had a sequential design with a planned accrual of 90 patients. Criteria for entry into the trial were: a unicentric, clinical TI infiltrating ductal, mucinous or tubular carcinoma without an extensive intraductal component or lymphatic vessel invasion; a wide excision with a pathologically-documented negative margin of at least 1 cm; and histologically negative axillary lymph nodes. No adjuvant RT or systemic therapy was administered. Seventy-six per cent of the lesions were detected by mammography alone. The median gross pathologic tumor size was 0.9 cm. The median patient age was 67 years. RESULTS: Eighty-seven patients were enrolled in the trial before it closed prematurely in 1992 because the predefined stopping boundary was crossed (i.e., the sixth local recurrence was observed). At that time, the average annual local recurrence rate was 4.2%. With a median follow-up of 56 months, there are now 14 patients (16%) with local recurrence as their site of first failure (average annual local recurrence rate: 3.6%). Four patients without local recurrence developed distant metastases. Three patients have died, one of metastatic breast cancer and two of unrelated causes. CONCLUSIONS: Even in a highly selected group of patients with early-stage breast cancer, there is a substantial risk of early local recurrence for those treated with wide excision alone.
Adenocarcinoma, Mucinous↗
High-dose chemotherapy for metastatic breast cancer.
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Breast Neoplasms↗
Fifteen-year results of breast-conserving surgery and definitive breast irradiation for the treatment of ductal carcinoma in situ of the breast.
PURPOSE: To determine the 15-year outcome for women with ductal carcinoma in situ (DCIS, intraductal carcinoma) of the breast treated with breast-conserving surgery followed by definitive breast irradiation. PATIENTS AND METHODS: An analysis was performed of 270 intraductal breast carcinomas in 268 women from 10 institutions in Europe and the United States. In all patients, breast-conserving surgery included complete gross excision of the primary tumor followed by definitive breast irradiation. When performed, pathologic axillary lymph node staging was node-negative (n=86). The median follow-up time was 10.3 years (range, 0.9 to 26.8). RESULTS: The 15-year actuarial overall survival rate was 87%, and the 15-year actuarial cause-specific survival rate was 96%. The 15-year actuarial rate of freedom from distant metastases was 96%. There were 45 local recurrences in the treated breast, and the 15-year actuarial rate of local failure was 19%. The median time to local failure was 5.2 years (range, 1.4 to 16.8). A number of clinical and pathologic parameters were evaluated for correlation with local failure, and none were predictive for local failure (all P > or = .15). CONCLUSION: The results from the present study demonstrate high rates of overall survival, cause-specific survival, and freedom from distant metastases following the treatment of DCIS of the breast using breast-conserving surgery and definitive breast irradiation. These results support the use of breast-conserving surgery and definitive breast irradiation for the treatment of DCIS of the breast.
Adult↗
Selection of patients with early stage invasive breast cancer for treatment with conservative surgery and radiation therapy.
The combination of breast-conserving surgery and radiation therapy is now accepted as a standard treatment option for most women with clinical stage I or II invasive breast cancer. The great majority of individuals with early stage breast cancer are potential candidates for treatment with conservative surgery and radiation therapy. Nonetheless, for a few patients, such treatment may be absolutely or relatively contraindicated due to toxicity concerns, poor anticipated cosmetic results, or a heightened risk of local failure. This article will discuss the patient, clinical, and pathologic factors relevant to selecting patients for this treatment approach.
Breast Neoplasms↗
Axillary lymph nodes and breast cancer: a review.
BACKGROUND: The value of surgical staging and treatment of the axillary lymph nodes with either surgery or radiotherapy in the initial management of patients with Stage I or II invasive breast cancer is controversial. METHODS: A review of retrospective and prospective clinical studies was performed to assess the risks of axillary lymph node involvement and the effectiveness and morbidity of various treatment options. RESULTS: The risk of axillary lymph node involvement is substantial for most patients, even those with small tumors. The morbidity resulting from a careful Level I/II axillary dissection or moderate-dose axillary radiotherapy is limited. Such treatment is highly effective in preventing axillary recurrence. The symptoms resulting from axillary failure can be controlled in many, but not all, patients. The available data suggest, but do not prove, that the initial use of effective axillary treatment may result in a small improvement in long term outcome in some patient subgroups. CONCLUSIONS: Most patients should be treated with either axillary surgery or irradiation. Highly selected subgroups of patients may have such low risks of involvement that specific axillary treatment is of little value. However, such subgroups have not yet been well defined. Treatment approaches that do not involve specific axillary treatment should be considered investigational at present, and the patients should be informed as to their potential risks. Prospective clinical studies of these issues should be pursued.
Arm↗
Long-term outcome following breast-conserving surgery and radiation therapy.
PURPOSE: To examine the long-term pattern and frequency of recurrences after breast-conserving therapy and whether the outcome was influenced by the era of treatment. METHODS AND MATERIALS: From 1968 to 1986, 1870 patients with unilateral Stage I or II breast cancer were treated at the Joint Center for Radiation Therapy. Of these, 1628 underwent gross tumor excision and received a dose of > 60 Gy to the tumor bed and constituted the study population. Patients were classified as without evidence of disease, dead from other causes (DOC), or by their first site of recurrence. First sites of recurrent disease were categorized as distant/regional (DF/RNF) or local (LR). Local recurrence was defined as the detection of any invasive or in situ carcinoma occurring in the ipsilateral breast and was further categorized as: true recurrence (TR), marginal miss (MM), skin recurrence (S), or elsewhere in the breast (E). Median follow-up in survivors was 116 months. Eighty patients (4.9%) were lost to follow-up at 3-175 months. The population was divided into two time cohorts: 1968-1982 (n = 810), with a median follow-up time of 143 months, and 1983-1986 (n = 792), with a median follow-up time of 95 months. RESULTS: The overall crude rates of ipsilateral breast recurrence were 7.4 and 13.3% at 5 and 10 years, respectively. Crude rates at 5 and 10 years were 5.7 and 9.3% for TR/MM and were 0.9 and 2.8% for E recurrences, respectively. The annual incidence rates for all LR ranged from 0.5-2.4% and was relatively constant after the first year. The annual incidence rates for TR/MM ranged from 0.4 to 1.9%, whereas for E recurrences the range was 0.1-0.7%. The crude rates of DF/RNF were 16.6 and 23.1% at 5 and 10 years, respectively. The annual incidence rates for DF/RNF ranged from 1-5% over all years. Although the magnitude of the incidence was different, DF/RNF recurrence predominated in years 1-3 for both node-positive and node-negative patients. For the 1968-1982 and 1983-1986 cohorts, the 5-year crude rates of ipsilateral breast recurrence were 8.8 and 5.9%, respectively. CONCLUSIONS: Distant and regional nodal failures were the predominant form of recurrence. The annual incidence rate of LR was relatively constant over the first decade. True recurrence/marginal miss was the most frequent type of ipsilateral breast recurrence and was highest during years 2 through 7. The risk of a recurrence elsewhere in the breast increased with longer follow-up and was highest during years 8 through 10. The 5-year crude rate of ipsilateral breast recurrence appeared lower in the 1983-1986 patient cohort compared to the 1968-1982 patient cohort (8.8% vs. 5.9%), but the distributions of site of first failure did not differ significantly (p = 0.13). Any decrease in ipsilateral breast recurrence likely reflects improvements in mammographic and pathologic evaluation, patient selection, and the increased use of reexcision.
Adult↗
Radiotherapy and management of the axilla in early breast cancer.
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Axilla↗
Conservative surgery without radiotherapy in the treatment of patients with early-stage invasive breast cancer. A review.
OBJECTIVE: The authors determined whether some patients with clinical stage I or II invasive breast cancer can be adequately treated by conservative surgery without radiotherapy. SUMMARY BACKGROUND DATA: Currently, there are many patients who are being treated in this manner in both academic and community hospitals. This approach is not as effective as either mastectomy or conservative surgery followed by radiotherapy in preventing local recurrence. However, there may be subsets of patients who might be adequately treated by surgery alone with acceptably low recurrence rates. METHODS: The authors reviewed retrospective studies of conservative surgery alone and of randomized trials comparing the results of treatment with and without postoperative radiotherapy. RESULTS: The local recurrence rate is unacceptably high when random patients are treated with conservative surgery without radiotherapy. More favorable results may be possible when relatively wide excisions are performed on selected postmenopausal patients with small lesions without an extensive intraductal component, lymphatic or blood-vessel invasion, and histologically negative axillary nodes. The role of tamoxifen in reducing the risk of breast recurrence is uncertain. Despite salvage therapy, some individuals may develop disseminated disease as a result of local recurrence. CONCLUSIONS: The authors believe that conducting carefully designed prospective studies of conservative surgery alone is reasonable for patients who are adequately informed of the potential risks of omitting radiation therapy. However, currently, patients should not be treated with conservative surgery alone (without radiotherapy) without such stringent guidelines.
Adult↗
The return (?) of postmastectomy radiotherapy.
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Breast Neoplasms↗
The role of radiation therapy in treating patients with potentially resectable carcinoma of the esophagus.
Radiotherapy (RT) in conjunction with surgery may have a number of roles in the treatment of patients with potentially resectable esophageal carcinoma. The use of RT alone either preoperatively or postoperatively can be expected to improve resectability rates only modestly. The risk of locoregional failure, a common problem in esophageal carcinoma, has been substantially reduced with preoperative or postoperative RT in trials with a duration of follow-up of 3 or more years, although this effect has not been seen in trials with shorter follow-up. Because of the high risk of distant failure associated with these tumors and perhaps because of the inadequate doses used, most trials of RT have not shown notable improvements in overall survival rates. The risk of severe complications following preoperative or postoperative RT is small, provided that very high doses or fraction sizes are avoided. Concurrent chemotherapy and RT administration have been shown to be superior to RT alone in patients who have medically or surgically inoperable conditions; randomized trials using this combined modality in patients with resectable disease have only recently begun. In addition to evaluating the efficacy of this approach, investigators hope to establish the optimal sequencing and timing of administration of these modalities with regard to each other and to surgery.
Chemotherapy, Adjuvant↗
The relationship between microscopic margins of resection and the risk of local recurrence in patients with breast cancer treated with breast-conserving surgery and radiation therapy.
BACKGROUND: The relationships among the involvement of tumor at the final margins of resection, the presence of an extensive intraductal component (EIC), and the risk of local recurrence are important considerations in patients treated with conservative surgery and radiation therapy for early stage breast cancer but have not been defined adequately. METHODS: Between 1982 and 1985, 885 patients were treated for clinical Stage I or II invasive breast cancer. The study population was limited to 181 patients with an infiltrating ductal carcinoma who received a radiation dose to the surgical site of 60 Gy or greater, whose final microscopic margins of resection were evaluable, and who had at least 5 years of follow-up. A positive margin was defined as tumor present at the inked margin of resection, a close margin as tumor within 1 mm of the inked margin, and a negative margin as no tumor within 1 mm of the inked margin. A focally positive margin was defined as tumor at the margin in three or fewer low-power fields. In 157 patients (87%), the tumor was evaluable for the presence or absence of an EIC. The median follow-up was 86 months. RESULTS: In 12 of 181 patients (7%), a recurrence developed at or near the primary site (true recurrence/marginal miss [TR/MM]) within 5 years. The 5-year rate of TR/MM (with 95% confidence intervals) among patients with negative, close, focally positive, and more than focally positive margins was 0% (0-4%), 4% (0-20%), 6% (1-17%) and 21% (10-37%), respectively. Patients with positive margins also were more likely to have a distant failure within 5 years (14%, 8%, 25%, and 32% in the four groups, respectively). However, patients with positive margins more often had positive axillary lymph nodes than patients with negative or close margins (59% vs. 38%, P < 0.02). The 5-year rate of TR/MM was 20% for patients with an EIC-positive tumor and 7% for patients with an EIC-negative tumor. However, among the 127 patients with an EIC-negative tumor, the 5-year rate of TR/MM was less than 10% in all margin groups. Among the 30 patients with an EIC-positive tumor, the 5-year rate of TR/MM was 0% when margins were negative or close but 50% when margins were more than focally positive. CONCLUSIONS: These results provide support for the use of breast-conserving surgery and breast irradiation in all patients with uninvolved margins, whether the tumor is EIC-positive or EIC-negative. This study suggests that breast-conserving therapy (including a radiation boost to the primary site) also may be a reasonable option for some patients with an EIC-negative tumor and margin involvement.
Breast↗
Salvage treatment for local recurrence following breast-conserving surgery and definitive irradiation for ductal carcinoma in situ (intraductal carcinoma) of the breast.
PURPOSE: The purpose of the present study is to evaluate the outcome of salvage treatment for local recurrence in the breast following the initial treatment of ductal carcinoma in situ (intraductal carcinoma) with breast-conserving surgery and definitive breast irradiation. METHODS AND MATERIALS: An analysis was performed of 42 local failures in the breast that occurred following the initial treatment of ductal carcinoma in situ (intraductal carcinoma) with breast-conserving surgery and definitive breast irradiation. At the time of the local recurrence, 23 cases (55%) showed invasive ductal carcinoma, and 19 cases (45%) showed intraductal carcinoma, one with associated Paget's disease. The surgical treatment at the time of local recurrence included mastectomy (n = 39), excision (n = 2), or other (n = 1). Adjuvant systemic therapy at the time of local recurrence included chemotherapy (n = 2), hormonal treatment (n = 7), both (n = 1), or none (n = 32). The median follow-up after salvage treatment was 3.7 years (mean = 4.0 years; range = 0.1-9.5 years). RESULTS: The 5-year actuarial outcome following salvage treatment for the 42 local recurrences showed an overall survival rate of 78% and a cause-specific survival rate of 84%. The 5-year actuarial rate of freedom from distant metastases was 86%. None of the patients with histology of the local recurrence of intraductal carcinoma or with detection of the local recurrence with mammographic findings only developed distant metastatic disease after salvage treatment. The 5-year actuarial rate of freedom from chest wall recurrence following salvage mastectomy was 92%. All three of the patients who developed chest wall recurrence following salvage mastectomy also developed distant metastatic disease. CONCLUSIONS: These results demonstrate that local recurrences following the initial treatment of ductal carcinoma in situ with breast-conserving surgery and definitive breast irradiation can be salvaged with high rates of survival, freedom from distant metastases, and freedom from chest wall recurrence. The results of salvage treatment support the use of breast-conserving surgery and definitive breast irradiation for the initial management of ductal carcinoma in situ of the breast.
Adult↗
The relation between the surgery-radiotherapy interval and treatment outcome in patients treated with breast-conserving surgery and radiation therapy without systemic therapy.
PURPOSE: This analysis was performed to clarify the relationship between the surgery-radiotherapy interval and the risk of recurrence in patients treated with breast-conserving therapy for early stage invasive cancers. METHODS AND MATERIALS: We retrospectively analyzed data from 653 patients with American Joint Commission on Cancer Stage I or II, pathologically node-negative breast cancer treated by breast-conserving therapy without adjuvant systemic therapy between 1968 and 1985. All patients received a dose of at least 60 Gy to the tumor bed. Two hundred and eighty-three patients started radiotherapy within 4 weeks of surgery, 308 started 5-8 weeks after surgery, and 54 started 9-12 weeks after surgery. Median follow-up in the 531 survivors was 100 months. RESULTS: Pathologic features and treatment characteristics were well balanced between the groups with surgery-radiotherapy intervals of 0-4 weeks and 5-8 weeks. There was no statistically difference in the risk of overall recurrence among patients starting radiotherapy 5-8 weeks after surgery compared with those treated within 4 weeks. Analysis of the 5-year crude rates of failure further demonstrated no difference in the distribution of sites of failure in the 5-8 week group compared with the 0-4 week group. A multivariate model controlling for known risk factors, as well as potential treatment-related confounders, also failed to demonstrate an increased risk of recurrence with the longer surgery-radiotherapy interval (risk ratio = 0.89, p = 0.44). CONCLUSION: This retrospective analysis suggests that a delay of up to 8 weeks in the interval between the last breast surgery and the start of radiotherapy is not associated with an increased risk of recurrence in patients with early stage breast cancer treated with breast irradiation to at least 60 Gy without systemic therapy.
Analysis of Variance↗