Refined estimates of local recurrence risks by DCIS score adjusting for clinicopathological features: a combined analysis of ECOG-ACRIN E5194 and Ontario DCIS cohort studies.

PURPOSE: Better tools are needed to estimate local recurrence (LR) risk after breast-conserving surgery (BCS) for DCIS. The DCIS score (DS) was validated as a predictor of LR in E5194 and Ontario DCIS cohort (ODC) after BCS. We combined data from E5194 and ODC adjusting for clinicopathological factors to provide refined estimates of the 10-year risk of LR after treatment by BCS alone. METHODS: Data from E5194 and ODC were combined. Patients with positive margins or multifocality were excluded. Identical Cox regression models were fit for each study. Patient-specific meta-analysis was used to calculate precision-weighted estimates of 10-year LR risk by DS, age, tumor size and year of diagnosis. RESULTS: The combined cohort includes 773 patients. The DS and age at diagnosis, tumor size and year of diagnosis provided independent prognostic information on the 10-year LR risk (p ≤ 0.009). Hazard ratios from E5194 and ODC cohorts were similar for the DS (2.48, 1.95 per 50 units), tumor size ≤ 1 versus  > 1-2.5 cm (1.45, 1.47), age ≥ 50 versus < 50 year (0.61, 0.84) and year ≥ 2000 (0.67, 0.49). Utilization of DS combined with tumor size and age at diagnosis predicted more women with very low (≤ 8%) or higher (> 15%) 10-year LR risk after BCS alone compared to utilization of DS alone or clinicopathological factors alone. CONCLUSIONS: The combined analysis provides refined estimates of 10-year LR risk after BCS for DCIS. Adding information on tumor size and age at diagnosis to the DS adjusting for year of diagnosis provides improved LR risk estimates to guide treatment decision making.

Intraductal carcinoma of the breast: results of treatment with excisional biopsy and irradiation.

Between 1976 and 1983, 40 women with intraductal carcinoma of the breast without invasion underwent excisional biopsy and irradiation as an alternative to mastectomy. The median age was 53 years (range, 28 to 77 years) and the median follow-up time since initiation of radiation was 44 months (range, 14 to 97 months). Twenty-seven patients presented with a palpable mass; in 13 patients the tumor was detected only by mammography. A limited axillary dissection was performed in 13 patients, and all lymph nodes removed were negative. Treatment was administered to the breast and adjacent chest wall to a dose of 4,600 to 5,000 rad, with 26 patients also receiving a boost dose of 1,000 to 2,000 rad to the site of the primary. Four patients have developed a recurrence in the treated breast, at 17, 19, 35, and 63 months after the beginning of radiation therapy. The 5-year actuarial rate of local recurrence is 10%. Three of the recurrences were in those four patients who presented with a nipple discharge and a central primary. In two cases, the recurrence consisted of only intraductal carcinoma; in the other two, both intraductal and invasive cancer were found. All four patients with recurrence underwent mastectomy and are well without evidence of distant metastases at 1, 12, 15, and 15 months since mastectomy. Cosmetic results were excellent. No patient has developed distant metastases. Since the number of patients treated is small and the period of follow-up is short, one must be cautious in the interpretation of these results. Nonetheless, the treatment of intraductal carcinoma of the breast by excision and irradiation appears to give acceptable local control and excellent survival when suitable precautions of patient selection and evaluation are taken.

Locoregional failure 10 years after mastectomy and adjuvant chemotherapy with or without tamoxifen without irradiation: experience of the Eastern Cooperative Oncology Group.

PURPOSE: To assess patterns of failure and how selected prognostic and treatment factors affect the risks of locoregional failure (LRF) after mastectomy in breast cancer patients with histologically involved axillary nodes treated with chemotherapy with or without tamoxifen without irradiation. PATIENTS AND METHODS: The study population consisted of 2,016 patients entered onto four randomized trials conducted by the Eastern Cooperative Oncology Group. The median follow-up time for patients without recurrence was 12.1 years (range, 0.07 to 19.1 years). RESULTS: A total of 1,099 patients (55%) experienced disease recurrence. The first sites of failure were as follows: isolated LRF, 254 (13%); LRF with simultaneous distant failure (DF), 166 (8%); and distant only, 679 (34%). The risk of LRF with or without simultaneous DF at 10 years was 12.9% in patients with one to three positive nodes and 28.7% for patients with four or more positive nodes. Multivariate analysis showed that increasing tumor size, increasing numbers of involved nodes, negative estrogen receptor protein status, and decreasing number of nodes examined were significant for increasing the rate of LRF with or without simultaneous DF. CONCLUSION: LRF after mastectomy is a substantial clinical problem, despite the use of chemotherapy with or without tamoxifen. Prospective randomized trials will be necessary to estimate accurately the potential disease-free and overall survival benefits of postmastectomy radiotherapy for patients in particular prognostic subgroups treated with presently used and future systemic therapy regimens.

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.

Postmastectomy radiotherapy: clinical practice guidelines of the American Society of Clinical Oncology.

OBJECTIVE: To determine indications for the use of postmastectomy radiotherapy (PMRT) for patients with invasive breast cancer with involved axillary lymph nodes or locally advanced disease who receive systemic therapy. These guidelines are intended for use in the care of patients outside of clinical trials. POTENTIAL INTERVENTION: The benefits and risks of PMRT in such patients, as well as subgroups of these patients, were considered. The details of the PMRT technique were also evaluated. OUTCOMES: The outcomes considered included freedom from local-regional recurrence, survival (disease-free and overall), and long-term toxicity. EVIDENCE: An expert multidisciplinary panel reviewed pertinent information from the published literature through July 2000; certain investigators were contacted for more recent and, in some cases, unpublished information. A computerized search was performed of MEDLINE data; directed searches based on the bibliographies of primary articles were also performed. VALUES: Levels of evidence and guideline grades were assigned by the Panel using standard criteria. A "recommendation" was made when level I or II evidence was available and there was consensus as to its meaning. A "suggestion" was made based on level III, IV, or V evidence and there was consensus as to its meaning. Areas of clinical importance were pointed out where guidelines could not be formulated due to insufficient evidence or lack of consensus. RECOMMENDATIONS: The recommendations, suggestions, and expert opinions of the Panel are described in this article. VALIDATION: Seven outside reviewers, the American Society of Clinical Oncology (ASCO) Health Services Research Committee members, and the ASCO Board of Directors reviewed this document.

Effect of radiotherapy after breast-conserving treatment in women with breast cancer and germline BRCA1/2 mutations.

PURPOSE: Recent laboratory data suggest a role for BRCA1/2 in the cellular response to DNA damage. There is a paucity of clinical data, however, examining the effect of radiotherapy (RT), which causes double-strand breaks, on breast tissue from BRCA1/2 mutation carriers. Thus the goals of this study were to compare rates of radiation-associated complications, in-breast tumor recurrence, and distant relapse in women with BRCA1/2 mutations treated with breast-conserving therapy (BCT) using RT with rates observed in sporadic disease. PATIENTS AND METHODS: Seventy-one women with a BRCA1/2 mutation and stage I or II breast cancer treated with BCT were matched 1:3 with 213 women with sporadic breast cancer. Conditional logistic regression models were used to compare matched cohorts for rates of complications and recurrence. RESULTS: Tumors from women in the genetic cohort were associated with high histologic (P =.0004) and nuclear (P =.009) grade and negative estrogen (P=.0001) and progesterone (P=.002) receptors compared with tumors from the sporadic cohort. Using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity scoring, there were no significant differences in acute or chronic morbidity in skin, subcutaneous tissue, lung, or bone. The 5-year actuarial overall survival, relapse-free survival, and rates of tumor control in the treated breast for the patients in the genetic cohort were 86%, 78%, and 98%, respectively, compared with 91%, 80%, and 96%, respectively, for the sporadic cohort (P = not significant). CONCLUSION: There was no evidence of increased radiation sensitivity or sequelae in breast tissue heterozygous for a BRCA1/2 germline mutation compared with controls, and rates of tumor control in the breast and survival were comparable between BRCA1/2 carriers and controls at 5 years. Although additional follow-up is needed, these data may help in discussing treatment options in the management of early-stage hereditary breast cancer and should provide reassurance regarding the safety of administering RT to carriers of a germline BRCA1/2 mutation.

Cost of breast cancer treatment. A 4-year longitudinal study.

OBJECTIVE: To determine the longitudinal cost of the treatment of patients with breast cancer. METHODS: An analysis was performed of 200 women with 205 newly diagnosed breast cancers during 1989 in a health maintenance organization population (US Healthcare, Blue Bell, Pa). Medical records and claims data were analyzed for the total costs of medical care during the 4-year period after diagnosis. The costs over time were analyzed for clinical stage and use of mammography screening. RESULTS: The total costs of medical care during the 4-year period after diagnosis were strongly related to clinical stage at diagnosis, with higher total costs for patients with stages III to IV at diagnosis compared with patients with stages 0 to II at diagnosis. The cost for all stages of disease declined after years 1 to 2, with the exception of stage II, which increased slightly in years 3 to 4. The use of screening mammography was associated with a significant decrease in the cost of medical care during the 4-year study period. CONCLUSIONS: The goal of mammography screening programs should be to achieve downstaging to stages 0 to 1 to achieve reduction in breast cancer mortality and to reduce the overall consumption of health care resources for the treatment of breast cancer. These cost data should be considered within the framework of future cost-effective analysis for screening mammography programs.

The importance of mammographic screening relative to the treatment of women with carcinoma of the breast.

BACKGROUND: The use of mammographic screening for the early detection of breast cancer has been shown to reduce the mortality from breast cancer. However, the impact of mammographic screening relative to the local treatment of the breast (ie, breast-conservation treatment vs mastectomy) is not well established. METHODS: An analysis was performed of 206 newly diagnosed and treated breast cancers in 201 women identified in 1989 from a health maintenance organization (US Healthcare, Blue Bell, Pa). The 206 breast cancers were evaluated for eligibility for and actual local treatment of the breast with breast-conserving surgery and definitive breast irradiation as a function of mammographic screening for the early detection of breast cancer. RESULTS: Eligibility for local treatment of the breast with breast-conserving surgery and definitive breast irradiation was significantly increased for the breast cancers detected in women who had undergone mammographic screening compared with the breast cancers detected in women who had not undergone mammographic screening (88% vs 60%, respectively; P < .0001). For the breast cancers that were eligible on chart review for treatment with breast-conserving surgery and definitive breast irradiation, there was no significant difference in the actual local treatment of the breast with breast-conserving surgery and definitive breast irradiation for the eligible breast cancers detected in women who had undergone mammographic screening compared with the eligible breast cancers detected in women who had not undergone mammographic screening (44% vs 37%, respectively; P = .40); however, there was a statistically significant difference for the subgroup of women aged 50 years or more (49% vs 21%, respectively; P = .016). CONCLUSIONS: These results show that breast cancers detected in women who had undergone mammographic screening were more likely to be eligible for breast-conserving surgery and definitive breast irradiation compared with breast cancers detected in women who had not undergone mammographic screening. For women aged 50 years or more, there was a significant increase in the use of breast-conserving surgery and definitive breast irradiation for eligible breast cancers detected in women who had undergone mammographic screening compared with eligible breast cancers detected in women who had not undergone mammographic screening.

Palliative radiotherapy for metastatic malignant melanoma: brain metastases, bone metastases, and spinal cord compression.

The records of all patients receiving palliative radiotherapy for malignant melanoma metastatic to brain, to bone, or with spinal cord compression were reviewed. The median survival of 77 patients with brain metastases from the initiation of radiotherapy was 14 weeks. A statistically improved survival was observed only in the 10 patients who underwent subtotal to total resection of a solitary brain metastasis prior to radiotherapy (median = 36 weeks). No improved survival was observed in the 12 patients with a solitary brain metastasis treated by radiotherapy alone (median = 16 weeks). Multivariate analysis revealed that fraction size, total dose, patient age, sex, and duration of the interval between initial diagnosis and appearance of brain metastases did not significantly influence survival, but the use of chemotherapy was associated with a decreased survival. Twenty six patients with symptomatic and radiographic evidence of 39 bone metastases showed a palliative response rate of 85%. 18 of 20 bony lesions treated with high-dose-per-fraction (greater than or equal to 400 cGy) and 15 of 19 bony lesions treated with conventional fractionation (less than or equal to 300 cGy) were palliated. Total dose, patient age, sex, interval between initial diagnosis of malignant melanoma and the appearance of bone metastases, prior or concurrent chemotherapy, or lesion location did not significantly influence palliation. Seventeen patients were identified with symptomatic and myelographic evidence of spinal cord compression. Complete palliation was observed in 47% (8/17) and partial palliation was observed in 24% (4/17). The overall palliation response rate for neurologic symptoms due to spinal cord compression of 71% appeared to be independent of fraction size and total dose.

Definitive irradiation for early stage breast cancer: The University of Pennsylvania experience.

From 1977 to 1984, 552 breast cancers in 548 women were treated with definitive irradiation following breast-conserving surgery at the Hospital of the University of Pennsylvania and the Fox Chase Cancer Center. All patients had invasive carcinoma and were AJC clinical Stage I or II. Pathologic axillary lymph node staging was known for all cases. The 5-year actuarial survival for the entire group was 93% with an NED survival of 81%. The 5-year survival for clinical Stage I and II patients was 97 and 87%, respectively, with a corresponding NED survival of 87 and 73%, respectively. For pathologic Stage I and II patients, the corresponding survival figures were 97 and 89%, respectively, with NED survival rates of 86 and 76%, respectively. The overall 5-year actuarial local failure rate was 6%, and the rate of local only as the first failure was 3%. The overall local-regional failure rate was 13% with a local-regional only first failure rate of 8%. These results compare favorably with other reported series and contribute a substantial number of patients to the increasing experience with definitive irradiation following breast-conserving procedures. The relatively low incidence of breast recurrence may be related to the emphasis on integrating the surgical, pathologic, and radiotherapeutic aspects of treatments, as well as the emergence of a re-excision policy for patients at high risk to have residual tumor.

Breast recurrence and survival related to primary tumor location in patients undergoing conservative surgery and radiation for early-stage breast cancer.

Between 1977 and 1986, 886 pts with Stage I and II breast cancer underwent excisional biopsy, axillary dissection and radiation. Median follow-up was 5 years (range 2 months-13 years). The patients were divided into four groups according to the primary tumor location: 1) outer (495 patients), 2) inner (202 patients), 3) central (119 patients), and 4) subareolar (70 patients). Subareolar tumors were defined as those immediately beneath the nipple-areolar complex or within 2 cm of the areolar margin. The comparability of the groups was assed in terms of clinical T stage, patient age, histology, final pathologic margin status, estrogen and progesterone receptor status, pathologic nodal status, and use of adjuvant chemotherapy. There were no significant differences among the four groups in the distribution of these factors except for the pathologic nodal status (outer 38% positive nodes, inner 24%, central 23%, subareolar 31%) p = .0004. There were no significant differences in 5 year actuarial overall survival (91% vs 86% vs 92% vs 91%, p = .34), relapse-free (75% vs 74% vs 80% vs 79%, p = .77), or NED survival (82% vs 78% vs 87% vs 84%, p = .29) for the four groups. A separate analysis for pathologic node negative and node positive patients revealed similar findings. For node-negative patients, the 5 year actuarial overall survival was 93% vs 88% vs 94% vs 91% (p = .20), the relapse-free survival was 78% vs 76% vs 82% vs 79% (p = .49), and the NED survival was 86% vs 81% vs 88% vs 86% (p = .46). For node-positive patients, the 5 year actuarial overall survival was 87% vs 82% vs 84% vs 90% (p = .59), relapse-free survival was 69% vs 66% vs 77% vs 80% (p = .78), and NED survival was 75% vs 68% vs 85% vs 80% (p = .66). Patterns of first failure were also not significantly different among the four groups: local only first failure (7% vs 4% vs 5% vs 8%, p = .49), any local first failure, i.e., +/- simultaneous distant metastases (8% vs 5% vs 5% vs 9%, p = .61), regional only (2% vs 1% 1% vs 0%, p = .65), any regional (4% vs 3% vs 3% vs 3%), or distant metastases (11% vs 17% vs 9% vs 10%, p = .16). A separate analysis of node negative and node positive patients revealed similar findings.(ABSTRACT TRUNCATED AT 400 WORDS)

Observations on the predictive value of perfusion lung scans on post-irradiation pulmonary function among 210 patients with bronchogenic carcinoma.

As a component of treatment planning for thoracic irradiation (RT), 210 bronchogenic carcinoma patients seen at the Fox Chase Cancer Center from 1983 to 1990 underwent quantitative perfusion scans, superimposition of their RT treatment fields onto these scans, and pulmonary function testing. These studies were used to prospectively estimate the influence of the planned thoracic irradiation on pulmonary function, as measured by the forced expiratory volume in one second (FEV1). Among the 156 patients with unresected lesions, the mean pre-RT FEV1 was 1.71 +/- 0.67 liters (+/- standard deviation), and the mean percentage of total lung perfusion within the treatment field was 31.0 +/- 12.1%. Mean values for the 54 patients treated post-operatively were 1.79 liters (pre-RT FEV1) and 28.8% (% perfusion within RT field). Using this technique, the prospectively predicted post-RT FEV1 is the product of the pre-RT FEV1 (1% of total lung perfusion within the treatment field). The mean predicted post-treatment FEV1 for the nonoperative patients was 1.15 +/- 0.43 liters and 1.25 +/- 0.41 liters for the postoperative patients. Forty-three nonoperative and 19 postoperative patients had FEV1 determinations following RT, at a mean post-RT interval of 11 months for nonoperative patients and 23 months for post-operative patients. Among nonoperative patients, 53% had no change in post-RT FEV1, 19% improved, while 22% had readings declining toward the predicted value. Only 5% had readings below predicted. Among postoperative patients, 37% had no change or improvement, 37% declined toward the predicted, 10% declined to predicted, and 11% had values worse than predicted. This technique of superimposing RT fields onto lung perfusion scans predicts for a degree of pulmonary impairment which is observed in only a minority of patients (10%) and which is rarely exceeded (6%).

Age as a prognostic factor for patients treated with definitive irradiation for early stage breast cancer.

From 1977 to 1986, 88 breast cancers in 86 women age less than or equal to 35 years were treated with definitive irradiation following breast-conserving surgery. The records of these cases were reviewed and compared to 808 breast cancers in 798 women age greater than or equal to 36 years treated similarly during the same time period. All women had AJC clinical Stages I or II invasive carcinoma of the breast and had undergone an axillary surgical staging procedure to determine pathologic lymph node staging prior to receiving definitive radiotherapy. There was no statistical difference between the younger and older women in terms of 5-year actuarial overall survival (94% vs. 90%), NED survival (78% vs. 81%) or relapse-free survival (70% vs. 77%). Although the younger women tended to have an earlier pattern of failure, the difference between the actuarial percentage of failures at 5 years for the two age groups was not significantly different for local only first failure (9% vs. 5%), regional only first failure (6% vs. 3%), and local and regional only first failure (0% vs. 1%). Subset analyses also did not show a difference between the younger and older patients. Although longer follow-up will be needed to confirm these observations, our 5-year results show that younger patients less than or equal to age 35 do not have an adverse outcome in terms of survival, local control, or regional control when compared with older patients greater than or equal to age 36. Potential candidates for definitive irradiation following breast-conserving surgery should not be excluded for treatment solely on the basis of younger age less than or equal to 35 years.

Frequency, sites of relapse, and outcome of regional node failures following conservative surgery and radiation for early breast cancer.

Between 1970 and 1986, 990 patients underwent excisional biopsy and radiation for clinical Stage I or II breast cancer. A limited axillary dissection (levels I and II) was performed in 914 of these patients. The median follow-up was 40 months from the initiation of radiation. Thirty-one patients developed a regional node failure as their first site of recurrence either with (12 patients) or without (19 patients) simultaneous distant metastases. The median interval to recurrence was 27 months (range 4-59). The 5-year actuarial rate for an isolated regional node recurrence (without simultaneous distant metastases) was 3%. The most common site for a regional node failure was the axilla (17 patients) followed by the supraclavicular nodes (13 patients). Salvage therapy was effective for an axillary +/- breast failure with 10/14 patients alive with no evidence of disease. Prognosis was related to the site of recurrence as well as the presence or absence of distant metastases. The 5-year actuarial survival from initial treatment for all patients with a regional node failure was 63% with a 3-year actuarial survival of 57% from diagnosis of recurrence. Regional node failure was related to the number of axillary nodes removed at the time of dissection and patient age.

Early-stage bilateral breast cancer treated with breast-conserving surgery and definitive irradiation: the University of Pennsylvania experience.

PURPOSE: To determine whether patients with early-stage bilateral breast cancer can be treated with definitive irradiation following breast-conserving surgery with acceptable survival, local control, complications, and cosmesis. METHODS AND MATERIALS: During the period 1977-1992, 55 women with Stage 0, I, or II concurrent (n = 12) or sequential (n = 43) bilateral breast cancer were treated with definitive irradiation following breast-conserving surgery. The records of these 55 patients with 110 treated breasts were reviewed for tumor size, histology, pathologic axillary lymph node status, first and overall site(s) of failure, and adjuvant chemotherapy or hormonal therapy. Curves for survival, local control, and regional control were determined. Cosmetic outcome, complication rates, and matching technique were analyzed. The median total radiation dose delivered was 64 Gy (range 42-72) using tangential whole-breast irradiation followed by an electron or iridium implant boost. The tangential fields were matched with no overlap in 40 patients (73%); there was overlap on skin of up to 4 cm in 14 patients (25%); and the matching technique was unknown in 1 patient (2%). The median follow-up for the 12 women with concurrent bilateral breast cancer was 4.0 years. The median follow-up for the other 43 women with sequential cancer was 9.3 and 4.9 years, respectively, after the first and second cancers. RESULTS: For the overall group of 55 patients, the 5- and 10-year overall survival rates were 96% and 94%, respectively, after treatment of the first cancer, and 96% and 92%, respectively, after treatment of the second cancer. The 5- and 10-year actuarial relapse-free survival rates were 90% and 75%, respectively, after treatment of the first cancer, and 83% and 72%, respectively, after treatment of the second cancer. For the 110 treated breast cancers, the 5- and 10-year actuarial local failure rates were 5% and 15%, respectively. Complication rates were: 28% breast edema, 8% arm edema, 4% pneumonitis, 3% cellulitis, 1% rib fracture, and 1% brachial plexopathy; no patient developed matchline fibrosis. For patients with a minimum of 3 years of relapse-free follow-up, the rate of excellent or good cosmetic outcome for 104 treated breasts was 85%. CONCLUSION: Definitive irradiation after breast-conserving surgery is technically feasible for selected patients with concurrent or sequential early-stage bilateral breast cancer. Survival, local control, complication rates, and cosmetic outcomes appear comparable to historical reports of breast conservation treatment for unilateral disease. Bilateral definitive breast irradiation after breast-conservation surgery should be considered an acceptable alternative treatment to bilateral mastectomy for selected patients with concurrent or sequential early-stage bilateral breast cancer.

Preservation of cosmesis with low complication risk after conservative surgery and radiotherapy for ductal carcinoma in situ of the breast.

PURPOSE: Although the clinical outcome after treatment of ductal carcinoma in situ (DCIS) using breast-conservation surgery and radiation therapy has been well documented, little data has been reported on cosmetic outcome or treatment complications. Therefore, the present study was performed to evaluate cosmesis and complications after breast-conservation treatment for DCIS and to analyze various factors that might affect cosmesis and predispose to complications. METHODS AND MATERIALS: The records of 90 patients who were alive without evidence of disease with a 3-year minimum follow-up were evaluated for cosmetic results and treatment complications following breast-conservation surgery and radiation therapy for DCIS. Complete gross excision of the primary tumor had been performed in all patients. Additionally, 24 patients had undergone an axillary lymph node dissection in the earlier years of the study. The majority of the patients had received 50-50.4 Gy to the whole breast followed by an electron boost for a total dose of 60-66 Gy. RESULTS: The cosmetic results of 90 evaluable patients at 3 years were: excellent in 69 (77%), good in 19 (21%), and fair in 2 (2%). The cosmetic results of 64 evaluable patients at 5 years were: excellent in 46 (72%), good in 16 (25%), and fair in 2 (3%). Factors associated with worse cosmetic results were an increased volume of tissue excised (>70 cm3) and a negative ipsilateral breast biopsy after radiotherapy. Complications in the 24 patients with an axillary dissection were: arm edema (n = 6), cellulitis of the arm (n = 5), and axillary vein thrombosis (n = 1). Complications in the 66 patients without an axillary dissection were: cellulitis of the arm (n = 1) and cellulitis of the breast (n = 1). DISCUSSION: Breast-conservation surgery followed by radiation therapy achieved excellent or good cosmetic results in 98 and 97% of patients at 3 years and 5 years, respectively. Complications were associated primarily with axillary dissection, which is no longer standard practice, and complications were uncommon in patients without an axillary dissection. Therefore, patients currently treated for DCIS of the breast would be expected to have a high rate of excellent or good cosmetic outcome with a low risk of complications.

Ten-year results of the treatment of early-stage breast carcinoma in elderly women using breast-conserving surgery and definitive breast irradiation.

PURPOSE: The optimal management of breast cancer in elderly women is not well established. Therefore, the present study was undertaken to evaluate the outcome of breast cancer in elderly women treated with breast-conserving surgery and definitive breast irradiation. METHODS AND MATERIALS: An analysis was performed of 558 women age > or = 50 years treated with breast-conserving surgery and definitive breast irradiation for Stages I-II invasive carcinoma of the breast. Of the 558 total women, there were 173 elderly women > or = 65 years and a comparison group of 385 women age 50-64 years. Treatment for all women included complete gross excision of the primary tumor, pathologic axillary lymph node staging, and definitive breast irradiation. Adjuvant systemic chemotherapy was used in 18% (102 out of 558) of the overall group. Adjuvant tamoxifen was used in 17% (94 out of 558) of the overall group. The median follow-up after treatment was 6.2 years (mean = 6.4 years; range = 0.1-15.4 years). RESULTS: Elderly patients age > or = 65 years and patients age 50-64 years were both found to have tumors with adverse prognostic features, including clinical T2 lesions (43 vs. 34%, respectively; p = 0.055), estrogen receptor negativity (9 vs. 16%, respectively; p = 0.13), and progesterone receptor negativity (17 vs. 21%, respectively; p = 0.50). Pathologic axillary lymph node staging showed that 24% of the elderly women were node positive, including 8% with four or more positive nodes, which was not different from women age 50-64 years (p = 0.23). There was no difference between the two age groups for the rate of deaths from breast cancer at 10 years (13 vs. 13%, respectively; p = 0.71). However, there was a significant difference between the two age groups for the rate of deaths from intercurrent disease at 10 years (11 vs. 2%, respectively; p = 0.0006). There were no differences between the two age groups for the 10-year rates of overall survival (77 vs. 85%, respectively; p = 0.14), relapse-free survival (64 vs. 70%, respectively; p = 0.16), freedom from distant metastases (83 vs. 78%, respectively; p = 0.45), or local failure (13 vs. 12%, respectively; p = 0.60). CONCLUSIONS: These results have shown that breast carcinomas in elderly women are not indolent and have a number of adverse prognostic features. Breast-conserving surgery and definitive breast irradiation in elderly women age > or = 65 years achieves good outcomes for survival, freedom from distant metastases, and local control, which are comparable to women age 50-64 years. The causes of deaths in elderly women age > or = 65 years are from both breast cancer and intercurrent disease. Breast-conserving surgery and definitive breast irradiation should continue to be considered as a standard treatment option for appropriately selected elderly women with early-stage breast cancer.

Outcomes in breast cancer patients relative to margin status after treatment with breast-conserving surgery and radiation therapy: the University of Pennsylvania experience.

PURPOSE: To evaluate the significance of final microscopic resection margin status on treatment outcomes in women with early breast cancer who are treated with breast-conserving surgery and definitive breast irradiation. METHODS AND MATERIALS: An analysis was performed of 1021 consecutive women with clinical Stage I or II invasive carcinoma of the breast treated with breast-conserving surgery and definitive breast irradiation. Complete gross excision of tumor was performed in all cases, and an axillary staging procedure was performed to determine pathologic axillary lymph node status. The 1021 patients were divided into four groups based on the final microscopic margin from the tumor excision or from the re-excision if performed. These four groups were: (a) 518 patients with negative margins; (b) 124 patients with focally positive margins; (c) 96 patients with focally close margins (< or = 2 mm); and (d) 283 patients with unknown margins. RESULTS: Local failure was not significantly different in patients with negative, focally positive, focally close or unknown final pathologic margins of resection at 8 years (8% vs. 10% vs. 17% vs. 16%, respectively, p = 0.21). The 8-year outcome also was not different among the four groups for overall survival (86% vs. 83% vs. 88% vs. 81%, respectively, p = 0.13), cause-specific survival (89% vs. 86% vs. 88% vs. 83%, respectively, p = 0.14), no evidence of disease survival (81% vs. 73% vs. 86% vs. 77%, respectively, p = 0.09), and freedom from distant metastases (85% vs. 75% vs. 86% vs. 79%, respectively, p = 0.08). CONCLUSION: These results demonstrate that selected patients with focally positive or focally close microscopic resection margins can be treated with breast-conserving surgery and definitive breast irradiation with 8-year local control rates and survival rates that are similar to those seen in breast-conservation patients with negative or unknown final resection margins.

Radiation therapy for chest wall recurrence of breast cancer after mastectomy in a favorable subgroup of patients.

PURPOSE: Long-term outcome after radiation therapy for local-regional recurrence of breast cancer after mastectomy is generally poor. This study was performed to evaluate the long-term outcome for a potentially favorable subgroup of patients with chest wall recurrence. METHODS AND MATERIALS: Of 71 patients with an isolated local-regional recurrence of breast cancer after mastectomy, 18 were identified who met the following favorable selection criteria: 1) a disease-free interval after mastectomy of 2 years or more, 2) an isolated chest wall recurrence, and 3) tumor size < 3 cm or complete excision of the recurrent disease. All 18 patients were treated with local-regional irradiation between 1967 and 1988. Radiotherapy (RT) was delivered to the chest wall to a median total dose of 60 Gy (range 30-66 Gy). Four patients received adjuvant chemotherapy and six patients received adjuvant hormonal therapy. RESULTS: With a median follow-up of 8.4 years, nine of 18 patients were alive and free of disease. The 10-year actuarial overall and cause-specific survivals were 72% and 77%, respectively. The 10-year actuarial relapse-free survival and local control were 42% and 86%, respectively. CONCLUSION: Treatment for a local-regional recurrence of breast cancer after mastectomy in a favorable subgroup of patients results in a high rate of long-term survival as well as excellent local control. Aggressive treatment is warranted in this favorable subgroup of patients.

Ten year results of conservative surgery and irradiation for stage I and II breast cancer.

Between 1977 and 1985, 697 women with clinical Stage I or II invasive breast cancer underwent excisional biopsy, axillary dissection, and definitive irradiation. Reexcision of the primary was performed in 330 and residual tumor was identified in 57% of these patients. Margins of resection were assessed in 50% and 257 had final margins of resection that were negative. Four hundred eighty patients had negative axillary dissections and 217 had histologically positive axillary nodes. Median follow-up was 58 months. The 10-year actuarial survival for the entire group was 83% with an NED survival of 73%. The 10-year actuarial survival was 87% for clinical Stage I and 77% for clinical Stage II patients with an NED survival of 79% and 67%, respectively. Patients with histologically negative axillary nodes had a 10-year overall survival of 86% (NED 78%) compared to 74% (NED 66%) for patients with positive nodes. Sixty-one patients developed a recurrence in the treated breast and in seven of these it was associated with simultaneous distant metastases. The cumulative probability of an isolated breast recurrence was 6% at 5 years and 16% at 10 years. The overall breast recurrence rate (+/- distant metastasis) was 8% at 5 years and 18% at 10 years. Breast recurrence was unrelated to T size, clinical stage, or histologic nodal status. The addition of adjuvant chemotherapy significantly decreased the risk of an isolated breast recurrence both at 5 and 10 years; however, there was no significant impact on the overall risk of a breast recurrence. Complications of treatment included moderate arm edema (5%), symptomatic pneumonitis (less than 1%), rib fraction (1%), pericarditis (0%), and brachial plexopathy (less than 1%). Cosmesis was judged to be good to excellent in 93% of patients in 10 years. These results have been achieved in a series of patients who for the most part have been treated by contemporary standards, that is, pathologic assessment of the axilla in all patients, reexcision in 47%, and adjuvant chemotherapy in 77% of node positive patients. Assessment of resection margins, however, was not performed in all patients (50%) and further follow-up in the group of patients with margin assessment will provide long term information on breast recurrence rate in this group of patients.