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HER2 (ERBB2) gene status serves as a strong predictive marker of response to HER2-targeted agents in invasive breast cancers, albeit with heterogeneous response. Our aim was to determine the distribution and prognosis of HER2 groups by fluorescent in situ hybridization (FISH) using the updated 2018 American Society of Clinical Oncology-College of American Pathologist (ASCO-CAP) guidelines. We identified 226 cases of equivocal or positive HER2 FISH invasive breast cancer (interpreted by ASCO-CAP guidelines at the time of reporting) who received HER2-targeted agents from 2006 to 2017. We subcategorized Group 1 further into three subgroups: low amplified (HER2/CEP17 ratio ≥ 2.0-2.99, mean HER2/cell 4.0-5.9), amplified (HER2/CEP17 ratio ≥ 2.0-2.99, mean HER2/cell ≥ 6), and excessive amplification (HER2/CEP17 ratio ≥ 3.0, mean HER2/cell ≥ 4.0). Outcomes studied were recurrence, metastasis, second breast primary, disease-specific survival (DSS), and overall survival (OS). Univariate analysis showed that the five categories of HER2 FISH were significantly associated with OS (p < 0.01), specifically higher HER2 amplification was associated with fewer deaths. HER2 FISH status also statistically significantly relates to DFS (p < 0.01) and metastasis (p = 0.01) but not with recurrence or second breast primary in our study. Tumor type and HER2 ISH Groups are independent predictors for both OS and DFS in our cohort. The proposed Group 1 subcategories were significantly associated with OS (p < 0.01) and DFS (p < 0.01), excessive HER2 amplification was associated with longer median survival. The Cox regression models showed better survival outcomes for the excessive amplification subgroup than the low amplified subgroup, with OS (hazard ratio = 0.63, 95% CI 0.42-0.93) and DFS (HR = 0.55, 95% CI 0.37-0.83). We demonstrated that in HER2 FISH Group 1 patients, high HER2 amplification was significantly associated with longer OS and DFS; these patients seem to benefit more from HER2-targeted regimens. We recommend reporting these Group 1 subcategories when assessing HER2 FISH.

The authors analyzed 52 cases of female breast angiolipoma (AL). Age distribution was 25 to 80 years of age (56.81 ± 12.78). Most cases showed vascularity below 50%, and 14 cases had vascularity >50%. Cellular and low-vascularity ALs had different clinical and radiological presentations. The mean size was 7.00 ± 3.62 mm for cellular ALs and 19.61 ± 7.58 mm for low-vascularity ALs. In any paucicellular area, the authors could identify a cluster of at least 3 interconnected vessels. The endothelium was mostly flat with uniform, hyperchromatic nuclei, and mitoses and nucleoli were absent. Fibrin thrombi in proliferating capillaries were noted in 96% of cases. Low-vascularity AL can be reliably distinguished on needle core biopsy from other lipomatous and vascular tumors of the breast. Tortuosity and proliferation of capillaries with at least 3 interconnected capillary channels in 1 focus with associated fibrin thrombi constitute a very strong clue for the diagnosis of AL on a breast needle core biopsy. Definite diagnosis of cellular AL is not always feasible because of rare cases with mitotic activity and cellular atypia. Excision is often recommended for cellular AL.

Objectives: A set of common epidemiologic risk factors have been associated with the risk of breast cancer despite of its molecular sub-classifications. We implemented a case series study with the primary objective of evaluating if obesity is associated with the diagnostic risk of "ER+ and/or PR+, HER2+", "ER-/PR-, HER2-", or "ER-/PR-, HER2+" relative to the most commonly diagnosed subtype of breast carcinoma, "ER+ and/or PR+, HER2-"., Methods: Demographic, clinical and pathologic data were collected from existing databases. The statuses of HER2/neu biomarker and hormone receptors were dichotomized as either positive or negative. Immunohistochemical staining was used to assess the prevalence of different subtypes. Body mass index was calculated from weight and height data collected at the time of consultation., Conclusions: Findings from the present study suggest that excess body weight decreases the diagnostic risk of "ER-/PR-, HER2-", or "ER-/PR-, HER2-" relative to "ER+ and/or PR+, HER2-". Obese and overweight women are more likely to be diagnosed with to "ER+ and/or PR+, HER2-", the subtype that has best prognosis and mostly associated with personal lifestyle. Weight gain with the population attributable-risk factor of 21.3% contributes the most to the incidence of invasive post menopausal breast cancer. Younger pre-menopausal women were more likely to be diagnosed with "ER+ and/or PR+, HER2+". In younger women biology of breast cancers with positive expression for hormone receptors and epidermal growth factor is a complex that extends beyond the currently assessed prognostic markers.

Objective: The primary objective of this study was to evaluate the race-specific risk associated with HER2/neu positive breast carcinoma in a prospective cohort design. Our secondary objectives were to assess prevalence of different breast cancer phenotypes between African-American and White women and to determine if race was associated with the risk of basal-like breast carcinoma phenotype in this cohort., Methods: Demographic, clinical and pathologic data were collected from existing databases. The status of HER2/neu and hormone receptors was dichotomized as either positive or negative. Immunohistochemistry taxonomy was used to assess prevalence of different breast carcinoma phenotypes. Risk estimates were calculated using the multivariable logistic regression statistics., Conclusions: The risk of HER2/neu positive breast carcinoma differs between African-American and White women. For White women only, this risk was statistically significant and increased almost linearly within each TNM stage with grade dedifferentiation. The statistically significantly higher prevalence of "ER(-)/PR(-), HER2(- )" phenotype in African American women potentially is the attributing factor to observed lack of an association between the risk of HER2/neu positive breast carcinoma with advanced stages and poorly differentiated grade. Among women diagnosed with "ER(-)/PR(-), HER2(-)" phenotype the odds ratios of being African-American and pre-menopausal was 1.72 (95% CI 1.17-2.54, P = 0.006) and 1.94 (95% CI 1.27-2.96, P = 0.002), respectively. The histologic features of basal-like and ER(-)/HER2(+ )carcinomas overlaps. Differences in the biology of breast carcinoma between African American and White women are partially attributed to the disparity in more adverse pathologic prognostic indicators at the initial clinical presentation of this disease.

Purpose: To determine the 15-year outcomes for women with early stage breast cancer after breast conservation therapy., Methods and Materials: Between 1977 and 1990, 937 women with Stage I and II breast carcinoma (55% T1N0, 16% T2N0, 18% T1N1, and 11% T2N1) underwent lumpectomy, axillary lymphadenectomy, and definitive irradiation. The median patient age was 52 years. Of the 937 patients, 375 (40%) received adjuvant chemotherapy and/or hormonal therapy, including 249 (92%) of the 270 women with pathologically positive nodes. The median follow-up was 10.1 years., Results: For the overall group, the 15-year overall survival rate was 71%, and the rate of freedom from distant metastases was 76%. The 15-year local failure rate was 19%. The 15-year contralateral breast cancer rate was 12%. The most common first events were distant failure (13%), local failure (10%), contralateral breast cancer (7%), and second malignant neoplasms (6%). The local failure rate at 10 years for favorable subsets of tumors characterized by mammographic detection, resection with negative margins, treatment with chemotherapy, and treatment with hormones was 8%, 10%, 10%, and 7%, respectively. Local failures were most commonly observed within (true recurrence), or just outside (marginal miss), the primary tumor bed (66%, 85 of 128). The rate of true recurrence or marginal miss at 5, 10, and 15 years was 5%, 10%, and 12%, respectively., Conclusion: These high rates of survival and local control confirm that breast conservation therapy yields favorable results in women with early breast cancer into the second decade after treatment.

Purpose: To evaluate the long-term outcome of combined modality therapy for inflammatory breast cancer., Methods and Materials: The data from 54 women treated between 1983 and 1996 for inflammatory breast cancer were analyzed. Patients with metastatic disease or disease progression on induction chemotherapy were excluded. Induction chemotherapy was given to 52 patients. Mastectomy was performed in 52 patients. Radiotherapy was delivered to the breast or chest wall and regional lymph nodes in all patients. The median follow-up for all patients was 5.1 years., Results: The 5- and 10-year overall survival rate was 56% and 35%, respectively; the corresponding relapse-free survival rates were 49% and 34%. Patients with a pathologic complete response after chemotherapy with or without preoperative radiotherapy had better 5- and 10-year overall survival rates (65% and 46%, respectively) and 5- and 10-year relapse-free survival rates (59% and 50%, respectively) compared with patients without a pathologic complete response. Those patients had a 5- and 10-year relapse-free survival rate of 45% and 27%, respectively. Locoregional failure at 5 and 10 years was 8% and 19%, respectively., Conclusion: The outcomes for patients completing multimodality therapy compare favorably with published data; however, the exclusion of patients with progression during induction chemotherapy may account in part for these results. The pathologic complete response rate was found to be an important prognostic factor. Selected patients with inflammatory breast cancer have the potential for long-term survival.

Purpose: The outcome for women with a local failure after breast conservation treatment is not well described in the literature. Because local recurrence is a potentially salvageable event, this study was performed to evaluate the outcome of patients with local recurrence after breast conservation surgery and definitive radiation treatment., Methods and Materials: The study population consisted of 112 patients with ipsilateral breast tumor recurrence. There were 100 isolated local recurrences and 12 local-plus-regional recurrences. There were 93 invasive local recurrences and 19 DCIS (ductal carcinoma in situ) local recurrences. Local recurrences were detected by physical examination alone in 42 patients, mammography alone in 47 patients, and both modalities in 23 patients. All patients were initially treated with breast conservation treatment with or without systemic therapy and subsequently treated at the time of local recurrence with salvage mastectomy with or without systemic therapy. The mean and median follow-up times after local recurrence were 49 and 44 months, respectively., Results: For the entire group of 112 patients, the overall survival at 10 years after local recurrence was 69%, the cause-specific survival was 71%, and the freedom from distant metastases was 47%. For the 93 patients with an invasive local recurrence, the overall survival at 10 years was 64%, cause-specific survival was 67%, and freedom from distant metastases was 44%. For the 93 patients with an invasive local recurrence, interval from diagnosis to local recurrence (< or =2 years vs. 2.1-5 years vs. >5 years) predicted for overall survival at 5 years (65% vs. 84% vs. 89%; p = 0.03). Method of detection of local recurrence (physical examination vs. mammography vs. both methods) also predicted for 5-year overall survival (73% vs. 91% vs. 93%, respectively; p = 0.04). On multivariable analysis, interval from diagnosis to local recurrence was an independent predictor of overall survival (p = 0.03). Method of detection of local recurrence (physical examination vs. mammography vs. both methods) was borderline in predicting for 5-year cause-specific survival (73% vs. 91% vs. 93%, respectively; p = 0.06). Similarly, interval from diagnosis to local recurrence (< or =2 years vs. 2.1-5 years vs. >5 years) was a borderline predictor of 5-year cause-specific survival (65% vs. 84% vs. 89%; p = 0.08). No factors that predicted for freedom from distant metastases were identified. There were three second locoregional failures on the chest wall. Two of the 19 patients with a DCIS local recurrence have died of metastatic breast cancer. Death was probably not related to their local recurrence, but rather a result of persistent risk from an invasive primary cancer., Conclusions: This analysis provides long-term data after salvage treatment for patients who experience local recurrence after breast conservation treatment. The variables of method of detection and interval from diagnosis to local recurrence are identified as having prognostic significance for overall and cause-specific survival. In view of the potential for long-term survival, aggressive attempt at salvage treatment is warranted for the patient with local recurrence after breast conservation treatment. Second local recurrence after salvage mastectomy is an uncommon event. Although DCIS local recurrences may not in themselves cause an increase in the risk of mortality, the risk from the primary invasive cancer persists.

Purpose: This study was performed to determine the long-term outcome for women with mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast treated with breast-conserving surgery followed by definitive breast irradiation., Methods and Materials: An analysis was performed of 422 mammographically detected intraductal breast carcinomas in 418 women from 11 institutions in North America and Europe. All patients were treated with breast-conserving surgery followed by definitive breast irradiation. The median follow-up time was 9.4 years (mean, 9.4 years; range, 0.1-19.8 years)., Results: The 15-year overall survival rate was 92%, and the 15-year cause-specific survival rate was 98%. The 15-year rate of freedom from distant metastases was 94%. There were 48 local failures in the treated breast, and the 15-year rate of any local failure was 16%. The median time to local failure was 5.0 years (mean, 5.7 years; range, 1.0-15.2 years). Patient age at the time of treatment and final pathology margin status from the primary tumor excision were both significantly associated with local failure. The 10-year rate of local failure was 31% for patient age < or = 39 years, 13% for age 40-49 years, 8% for age 50-59 years, and 6% for age > or = 60 years (p = 0.0001). The 10-year rate of local failure was 24% when the margins of resection were positive, 9% when the margins of resection were negative, 7% when the margins of resection were close, and 12% when the margins of resection were unknown (p = 0.030). Patient age < or = 39 years and positive margins of resection were both independently associated with an increased risk of local failure (p = 0.0006 and p = 0.023, respectively) in the multivariable Cox regression model., Conclusions: The 15-year results from the present study demonstrated high rates of overall survival, cause-specific survival, and freedom from distant metastases following the treatment of mammographically detected ductal carcinoma in situ of the breast using breast-conserving surgery and definitive breast irradiation. Younger age and positive margins of resection were both independently associated with an increased risk of local failure. The 15-year results in the present study serve as an important benchmark for comparison with other treatment modalities. These results support the use of breast-conserving surgery and definitive breast irradiation for the treatment of appropriately selected patients with mammographically detected ductal carcinoma in situ of the breast.

Background: The purpose of the current study is to evaluate the outcome of salvage treatment for local recurrence after breast-conserving surgery and radiation as initial treatment for mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast., Methods: An analysis was performed of 42 patients with local only first failure (n = 41) or local-regional only first failure (n = 1) after breast-conserving surgery and radiation treatment had been given for DCIS of the breast. Surgical treatment at the time of local recurrence included mastectomy (n = 37; 88%) or excision (n = 5; 12%). Adjuvant systemic therapy at the time of local recurrence was chemotherapy (n = 3; 7%), tamoxifen (n = 8; 19%), both (n = 1; 2%), none (n = 29; 69%), or unknown (n = 1; 2%). The median interval from the time of initial treatment to local recurrence was 4.8 years (range = 1.0-15.2 yrs). The median follow-up after salvage treatment was 4.5 years (range = 0.2-12.8 yrs)., Results: At the time of the local recurrence, 22 patients (52%) had invasive ductal carcinoma, 18 patients (43%) had DCIS, 1 patient (2%) had invasive lobular carcinoma, and 1 patient (2%) had angiosarcoma. After salvage treatment, the rate of overall survival and the rate of cause specific survival for all 42 patients were 92% at both 5- and 8-years after treatment. The rate of freedom from distant metastases was 89% at 5 and 8 years. Favorable prognostic factors after salvage treatment were DCIS as the histology of the local recurrence and mammography only as the method of detection of the local recurrence., Conclusions: The results of salvage treatment in the current study demonstrated that local recurrences were salvaged with high rates of survival and freedom from distant metastases. These results support the use of breast-conserving surgery and radiation for initial management of DCIS of the breast., (Copyright 2001 American Cancer Society.)

Purpose: The purpose of this study was to evaluate the relationship between a family history of breast or ovarian cancer and outcome after breast-conserving surgery and radiation in women presenting with an initial diagnosis of ductal carcinoma in situ (DCIS) of the breast., Methods and Materials: A total of 146 consecutive women with a pathologic diagnosis of ductal carcinoma in situ as their first diagnosis of any breast cancer were identified; 28 (19%) had a positive family history of breast or ovarian cancer in a first-degree relative, 27 (19%) had a positive family history in a second-degree relative, and 91 (62%) had no family history. Pathologic, clinical, and treatment factors, and clinical outcomes for each family history group were compared. Cosmesis and complications were recorded at each follow-up. Patients were treated between 1978 and 1995, and the median follow-up was 7.1 years., Results: Patients with a positive family history in a first- or second-degree relative each had an 8% incidence of local failure at 10 years, while the negative family history group demonstrated a 16% local failure rate (p = 0.33). Overall survival at 10 years for patients with a positive family history in a first- or second-degree relative was 100% and for those with a negative family history was 91% (p = 0.08). The negative family history group had a higher median age that may account for the difference in overall survival. Cause-specific survival (CSS) was 97%, 100%, and 99%, respectively, at 10 years (p = 0.25). There were no differences in the cosmetic results or complication rates between women with a positive or negative family history., Conclusion: We have shown that a family history of breast and/or ovarian cancer is not associated with an adverse outcome for women treated with breast conservation therapy for DCIS. Local recurrence, cause-specific survival, overall survival, cosmesis, and complication rates were comparable to that of similarly treated women with negative family histories. Therefore, a positive family history is not a contraindication for breast conservation therapy in women with DCIS.

Purpose: The success of adjuvant chemotherapy has prolonged the interval between surgery and postmastectomy radiation therapy for high-risk breast cancer patients. The purpose of this study is to determine whether a delay in radiation therapy after mastectomy results in an increased risk of local-regional recurrence of breast cancer., Materials and Methods: A retrospective review was performed of the University of Pennsylvania database of 221 patients with high-risk breast cancer treated with postmastectomy radiation therapy between 1977 and 1992. The surgery to postmastectomy radiation therapy time interval was 2 months or less in 82 patients (37%), 2.1 to 6 months in 50 patients (23%), and greater than 6 months in 89 patients (40%). Adjuvant chemotherapy was utilized in 151 patients (68%). The median follow-up was 4.3 years after postmastectomy radiation therapy., Results: Because the three groups showed significant differences for a number of prognostic factors, outcomes are reported in terms of local-regional recurrence only and not survival. The actuarial rate of local-regional recurrence at 8 years was 13% for patients with a surgery to radiation therapy interval of 2 months or less, 4% for those with an interval of 2.1 to 6 months, and 12% for those with an interval of greater than 6 months. A similar analysis performed for 4 months or less versus greater than 4 months between surgery and postmastectomy radiation therapy showed no difference in local-regional recurrence (11% versus 10%, respectively)., Conclusions: A delay in the institution of postmastectomy radiation therapy in favor of the prolongation of chemotherapy for high-risk breast cancer patients does not adversely affect outcome for local-regional recurrence at 8 years.

Rationale and Objectives: Bringing a new imaging technology to market is a complex process. Beyond conceptualization and proof of concept, obtaining U.S. Food and Drug Administration (FDA) approval for clinical use depends on the documented experimental establishment of safety and efficacy. In turn, safety and efficacy are evaluated in the context of the intended use of the technology. The purpose of this study was to examine a conceptual framework for technology development and evaluation, focusing on new breast imaging technologies as a highly visible and current case in point., Materials and Methods: The FDA views technology development in terms of a preclinical and four clinical phases of assessment. With a concept of research and development as a learning model, this phased-assessment concept of regulatory review against intended use was integrated with a five-level version of a hierarchy-of-efficacy framework for evaluating imaging technologies. Study design and analysis issues are presented in this context, as are approaches to supporting expanded clinical indications and new intended uses after a new technology is marketed., Conclusion: Breast imaging technologies may be intended for use as replacements for standard-of-care technologies, as adjuncts, or as complementary technologies. Study designs must be appropriate to establish claims of superiority or equivalence to the standard for the intended use. Screening technologies are ultimately judged on their demonstrated effectiveness in decreasing cause-specific mortality through early detection, but they may be brought to market for other uses on the basis of lesser standards of efficacy (eg, sensitivity, specificity, positive and negative predictive value, and stage of disease detected).

Magnetic resonance imaging (MRI) may be more sensitive than mammography for detecting breast cancer and may have an adjunctive role in assessing patients with early-stage disease for breast conservation treatment. This study was performed to analyze the impact of breast MRI on the clinical management of 83 patients being considered for breast conservation treatment. Eighty-three consecutive cases of patients undergoing breast MRI during standard workup and evaluation for breast conservation treatment from 1993 to 1996 were retrospectively reviewed. Records were reviewed for patient and tumor characteristics, mammographic findings, MRI findings, timing of MRI study, findings from MRI-guided surgery (when done), and whether the patient underwent breast conservation treatment. MRI definitely altered management in 15 patients (18%), may have affected management in 4 patients (5%), and did not change management in 64 patients (77%). Thirteen patients underwent additional surgery because of MRI findings; the positive predictive value for MRI-guided surgery was 38% (5 of 13). Ultimately, 82% of the patients received breast conservation treatment. No predictive factor was identified to characterize the patients most likely to have management affected by MRI findings. These findings suggest that breast MRI may be useful in the evaluation of patients with early-stage breast cancer for breast conservation treatment. A larger study population and outcome data will be required to confirm these findings and to define those patients most likely to benefit from breast MRI.

The patterns of treatment for newly diagnosed breast carcinomas in older women aged 65 years or more have not been well studied, particularly in relation to screening mammography performed for the early detection of breast cancer. Therefore, the present study was performed to determine the patterns of treatment for newly diagnosed breast carcinomas in older women aged 65 years or more and to determine the impact of screening mammography on these patterns of treatment. The study population consisted of 130 women aged 65 years or more with newly diagnosed breast carcinoma from 1993 through 1994 enrolled in a large health maintenance organization. The medical records of these 130 patients were reviewed. The breast cancers detected in women who had undergone mammographic screening were more often eligible for breast-conservation treatment than the breast cancers detected in women who had not undergone mammographic screening (79% vs. 48%, respectively; p = 0.0044). For the breast cancers that were eligible for breast-conservation treatment, breast-conservation treatment was used more often for the women who had undergone mammographic screening than for the women who had not undergone mammographic screening (70% vs. 27%, respectively; p = 0.0077). Definitive radiation therapy was delivered after breast-conservation surgery in 89% (55/62) of the patients. Medical oncology consultation was obtained more commonly for more advanced staged breast cancers. Clinical management was altered in 9% (12/130) of the patients because of older patient age, comorbid medical conditions, or both. These findings have documented the patterns of treatment for older women aged 65 years or more with newly diagnosed breast cancer. Screening mammography had a significant impact on the patterns of breast cancer management, as demonstrated by the association of screening mammography with an increased eligibility for breast-conservation treatment and an increased use of breast-conservation treatment for eligible patients.

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.

Purpose: Postmastectomy radiation therapy is often recommended for patients at high risk for local-regional recurrence after mastectomy. However, long-term outcomes after radiation therapy are not well described., Patients and Methods: Between 1977 and 1992, 221 patients at high risk for local-regional recurrence of breast cancer after mastectomy were treated with radiation therapy, with or without adjuvant systemic therapy. Patients were classified as high risk because of T3 or T4 tumors (14%), positive lymph nodes (29%), close or positive margins of resection (15%), or multiple risk factors (39%); 4% did not meet current criteria for radiation therapy. The median age of patients was 51 years. Radiation therapy consisted of 45 to 50.4 Gy to the chest wall in 1.8 to 2.0 Gy fractions. The regional lymph nodes were treated in 187 patients (85%). There were 151 patients (68%) who received adjuvant chemotherapy. Patients who received chemotherapy were younger (median age, 48 years vs 64 years) and had more positive lymph nodes (median, 5 vs 1) than patients not receiving chemotherapy. Adjuvant hormonal therapy was utilized in 116 patients (53%). The median follow-up was 4.3 years., Results: The actuarial 10-year local-regional failure rate was 11% (95% CI: 6.5% to 16.7%). The site of first failure was distant metastases in 75 patients (34%), local-regional recurrence in 11 patients (5%), and both sites in three patients (1%); 60% had no evidence of disease at last follow-up. Of the patients who presented with local-regional recurrence as first failure, nine patients (82%) subsequently developed metastatic disease. The median time to local-regional first failure was 1.3 years. The median time to distant metastases after local-regional first failure was 0.3 years., Discussion: Postmastectomy radiation therapy is associated with an 89% rate of local-regional control in this high-risk population. Patients who experience a local-regional recurrence after radiation therapy are at a very high risk for metastatic disease. Radiation therapy after mastectomy is recommended to optimize local-regional control for high-risk breast cancer 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.

Purpose: The present study reports the effects of patient age and family history on outcome after breast-conservation treatment. In addition, the interaction of age and family history is examined to determine outcome for younger patients with a positive family history of breast cancer (i.e., at a higher risk of having the BRCA1 or BRCA2 gene) after breast-conservation treatment., Patients and Methods: From 1977 to 1992, 1021 women underwent breast-conservation treatment for American Joint Committee on Cancer stage I and II breast cancer at the Hospital of the University of Pennsylvania. In all patients, breast-conservation treatment included complete gross excision of the primary tumor and axillary lymph node dissection, followed by definitive breast irradiation. When indicated, radiation to the regional lymphatics, adjuvant chemotherapy, and/or adjuvant hormones were given. Patients were divided for analysis into three age groups (< or = 40 years, 41 to 50 years, and > or = 51 years) as well as three family history groups (first-degree relative positive for breast cancer, other family history positive for breast cancer, and negative family history for breast cancer). Median follow-up after treatment was 6.1 years., Results: The 10-year actuarial overall survival rates were 74% for women aged < or = 40 years, 82% for women aged 41 to 50 years, and 82% for women aged > or = 51 years (P = 0.12). For the younger women, aged < or = 40 years, there was a higher 10-year rate of deaths from breast cancer (P = 0.007) but a lower rate of deaths from other causes (P = 0.08) than in the older two age groups. The younger women had a higher rate of local failure at 10 years compared with the two older age groups (22%, 18%, and 12%, respectively), but this difference was not statistically significant (P = 0.10). No significant differences were found between the three family history groups (first-degree relative positive for breast cancer, other family history positive for breast cancer, and negative family history for breast cancer) for survival, freedom from distant metastases, or local failure (all P > or = 0.25). For younger women, aged < or = 40 years, the 5-year outcomes for survival, freedom from distant metastases, and local failure were not different according to family history status (all P > or = 0.18). Similarly, the 5-year outcomes were not different according to family history status for women aged 41 to 50 years (all P > or = 0.46) and for women aged > or = 51 years (all P > or = 0.54)., Discussion: The present study has confirmed that breast-conservation treatment is suitable for appropriately selected younger patients or patients with a positive family history of breast cancer. Further, a positive family history of breast cancer in younger women does not represent a contraindication to breast-conservation treatment. In summary, younger age, positive family history of breast cancer, or younger age plus a positive family history of breast cancer should not preclude the use of breast-conservation treatment for appropriately selected patients.

Purpose: The optimal sequencing of chemotherapy and radiation therapy in patients with early-stage breast cancer undergoing breast-conservation treatment remains controversial. The purpose of this study is to evaluate the outcome of patients treated with one specific sequence of concurrent chemoradiation followed by additional chemotherapy., Methods: Between 1977 and 1992, 210 patients with stage I and II breast cancer underwent lumpectomy and axillary lymph node dissection followed by treatment with concurrent chemotherapy and radiation therapy, followed by further chemotherapy. Chemotherapy consisted of two 28-day cycles of CF (oral cyclophosphamide, 100 mg/m2 day 1 to 14, and intravenous 5-fluorouracil, 600 mg/m2 days 1 and 8) during radiation therapy, followed in general by six cycles of CMF (CF doses as above plus intravenous methotrexate 40 mg/m2 days 1 and 8) after the completion of radiation therapy. Fifty patients also received hormonal therapy, predominantly tamoxifen. One hundred ten patients had clinical T1 lesions, and 100 had T2 lesions. Fifty-three patients were pathologic N0, and 157 patients were pathologic N1 (123 patients had one to three positive nodes, and 34 patients had four or more positive nodes). Median follow-up for node-negative patients (5.2 years) is shorter than for node-positive patients (7.6 years). Therefore, outcome is reported at 5 and 10 years for node-positive patients but only at 5 years for node-negative patients., Results: For node-positive patients, outcomes at 5 and 10 years, respectively, were 86% and 70% for overall survival, 78% and 67% for no evidence of disease survival, and 82% and 69% for freedom from distant metastases. For node-negative patients, outcomes at 5 years were 94% for overall survival, 94% for no evidence of disease survival, and 94% for freedom from distant metastases. Pathologic nodal status was predictive of outcome after treatment. Local failure in the treated breast was 5% at 5 years and 13% at 10 years for all patients., Conclusions: Concurrent CF with radiation therapy followed by six cycles of CMF after radiation therapy results in excellent survival, freedom from distant metastases, and local control for both node-negative and node-positive patients. This regimen of concurrent chemotherapy and radiation therapy is one option for sequencing, and it avoids the delays in administration of either modality that are associated with other sequencing regimens.

We have identified a novel protein, BAP1, which binds to the RING finger domain of the Breast/Ovarian Cancer Susceptibility Gene product, BRCA1. BAP1 is a nuclear-localized, ubiquitin carboxy-terminal hydrolase, suggesting that deubiquitinating enzymes may play a role in BRCA1 function. BAP1 binds to the wild-type BRCA1-RING finger, but not to germline mutants of the BRCA1-RING finger found in breast cancer kindreds. BAP1 and BRCA1 are temporally and spatially co-expressed during murine breast development and remodeling, and show overlapping patterns of subnuclear distribution. BAP1 resides on human chromosome 3p21.3; intragenic homozygous rearrangements and deletions of BAP1 have been found in lung carcinoma cell lines. BAP1 enhances BRCA1-mediated inhibition of breast cancer cell growth and is the first nuclear-localized ubiquitin carboxy-terminal hydrolase to be identified. BAP1 may be a new tumor suppressor gene which functions in the BRCA1 growth control pathway.

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.

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.

Although claims data are increasingly being used to measure and manage the cost and quality of health care, few studies have evaluated algorithms developed for such analyses. Therefore, the present study was performed to evaluate prospectively a previously published algorithm used to identify women with the new diagnosis of carcinoma of the breast. This algorithm had been developed from the patterns of claims that suggested common clinical presentations of carcinoma of the breast. In the present study, this algorithm was used to identify 177 potential cases of women with newly diagnosed carcinoma of the breast from the claims database of a large health maintenance organization (HMO). The algorithm's positive predictive value for cases identified in the present study was 83% (147/177). To attempt to improve upon the positive predictive value, multiple modifications of the algorithm were performed. The previously defined best modification of the initial algorithm yielded a positive predictive value of 84% (147/174) in the present study with the loss of none of the true positive cases. These results demonstrate that logic-based algorithms can be used as a valid and efficient method of identifying large numbers of new breast cancer cases from claims data. This algorithm provides a powerful tool to perform health care analysis and research for women with newly diagnosed carcinoma of the breast.

Recent studies have identified mutations in the breast and (ovarian cancer susceptibility gene 2 (BRCA2), one which has been found in the germline of several males and one female affected with breast cancer. To establish the carrier frequency of this mutation in a large population of individuals affected with cancer, we evaluated constitutional DNA isolated from 83 individuals diagnosed with breast cancer and 93 diagnosed with ovarian cancer at any age, 42 of whom reported a family history of cancer. Using a simple allele-specific PCR-based nonradioactive method, we detected a total of eight individuals (4.5%) carrying a 1-bp deletion at nucleotide 6174 of the BRCA2 gene (6174delT). The age of disease onset in the mutant allele carriers was highly variable and typically late onset (41-72 years for breast cancer and 48-73 years for ovarian cancer). Evaluation of family histories for the eight mutant allele carriers revealed that several individuals had significant cancer histories that included, in addition to breast and/or ovarian cancer, an increased incidence of colon, esophageal, pancreatic, stomach, and hematopoietic cancers. Interestingly, seven of the eight individuals were of Ashkenazi Jewish descent. Haplotype data for the mutant allele carriers using markers spanning the region of the BRCA2 gene on chromosome 13ql2-ql3 suggest that only two of the confirmed Jewish Ashkenazi individuals share a single common ancestry, indicating several independent origins for this mutation. These data provide evidence for the presence of a specific BRCA2 mutation which has its origins in both Jewish Ashkenazi and non-Jewish populations. The observed overrepresentation of specific mutations within a subgroup of the general population may eventually help contribute to the development of inexpensive and routine tests such as the one described in our study.

Purpose: Chemotherapy plays an increasingly important role in the treatment of both node-negative and node-positive breast cancer patients, but the optimal sequencing of chemotherapy and radiation therapy is not well established. The purpose of this study is to evaluate the interaction of sequence and type of chemotherapy and hormonal therapy given with radiation therapy on the cosmetic outcome and the incidence of complications of Stage I and II breast cancer patients treated with breast-conserving therapy., Methods and Materials: The records of 1053 Stage I and II breast cancer patients treated with curative intent with breast-conserving surgery, axillary dissection, and radiation therapy between 1977-1991 were reviewed. Median follow-up after treatment was 6.7 years. Two hundred fourteen patients received chemotherapy alone, 141 patients received hormonal therapy alone, 86 patients received both, and 612 patients received no adjuvant therapy. Patients who received chemotherapy +/- hormonal therapy were grouped according to sequence of chemotherapy: (a) concurrent = concurrent chemotherapy with radiation therapy followed by chemotherapy; (b) sequential = radiation followed by chemotherapy or chemotherapy followed by radiation; and (c) sandwich = chemotherapy followed by concurrent chemotherapy and radiation followed by chemotherapy. Compared to node negative patients, node-positive patients more commonly received chemotherapy (77 vs. 9%, p < 0.0001) and/or hormonal therapy (40 vs. 14%, p < 0.0001). Among patients who received chemotherapy, the majority (243 patients) received concurrent chemotherapy and radiation therapy with two cycles of cytoxan and 5-fluorouracil (5-FU) administered during radiation followed by six cycles of chemotherapy with cytoxan, 5-fluorouracil and either methotrexate (CMF) or doxorubicin(CAF). For analysis of cosmesis, patients included were relapse free with 3 years minimum follow-up., Results: The use of chemotherapy had an adverse effect on cosmetic outcome compared to no chemotherapy, which was of borderline significance at 3 years (92% excellent or good cosmetic outcome vs. 96% respectively, p = 0.057); however, cosmesis was not different at 5 years (91 vs. 93% respectively, p = 0.67). Cosmesis was not significantly different between patients treated sequentially and those treated concurrently (3 year: 87 vs. 93% respectively, p = 0.33), nor was it different between patients who received CMF vs. CAF (3 year: 92 vs. 93% respectively, p = 0.89). Hormonal therapy did not influence cosmetic outcome (p = 0.78). The incidence of Grade 4 or 5 arm edema (> or = 2 cm difference in arm circumference) was 2% without chemotherapy vs. 8% with chemotherapy (p = 0.00002). However, the incidence of arm edema was not affected by sequencing or type of chemotherapy (all p > or = 0.52). Patients treated sequentially had a 10% incidence of Grade 4 or 5 arm edema vs. 7% in the patients treated concurrently (p = 0.52). The incidence was 7 vs. 9% in patients treated with CMF vs. CAF (p = 0.73). The incidence of clinical pneumonitis and rib fracture was not influenced by use of chemotherapy, sequence of chemotherapy or use of hormonal therapy (all p > or = 0.06)., Conclusions: Chemotherapy can be given concurrently with radiation therapy in the treatment of Stage I and II breast cancer with breast-conserving therapy without seriously compromising cosmetic outcome or incidence of complications compared to patients receiving other sequences of chemotherapy. Hormonal therapy did not affect cosmesis or complications. The chemotherapeutic regimen of cytoxan and 5-FU concurrent with radiation therapy followed by more chemotherapy is one reasonable option for breast conservation therapy in patients requiring chemotherapy.

We screened 163 women from breast-ovarian cancer-prone families, as well as 178 individuals affected with breast and/or ovarian cancer but unselected for family history, for germ-line mutations in exon 2 of BRCA1, by SSCP analysis and direct sequencing. A total of 25 mutations were detected. Thirteen of 64 Jewish Ashkenazi women and 2 non-Jewish individuals were found to possess the 185delAG mutation. Haplotype data for all 15 individuals, with markers intragenic to BRCA1, suggest that the Jewish Ashkenazi individuals share a common ancestry that is distinct from the lineage shared by the other two women. These data provide the first evidence of two distinct lines of transmission for the 185delAG mutation, only one of which has its origins in the Jewish Ashkenazi population. Our screening also uncovered 10 affected individuals with an 11-bp deletion at nucleotide 188 of BRCA1 (188del11), 4 of whom are Ashkenazi Jews. This is only the third reported mutation detected within the Jewish Ashkenazi population and may represent the second most common alteration in BRCA1 found in Ashkenazi Jews in the United States. The observed overrepresentation of specific mutations within a subgroup of the general population may eventually contribute to the development of inexpensive and routine tests for BRCA1 mutations, as well as to the elucidation of other contributory factors (e.g., diet, environment, and chemical exposures) that may play a key role in cancer initiation and development. The implications of the mutational data, as well as the role that founder effect, demographic history, and penetrance play in the resulting observed phenomena, are discussed.

Purpose: Ductal carcinoma in situ (DCIS) is increasingly detected as a nonpalpable lesion on mammographic screening performed for the early detection of breast cancer. Because of the growing incidence of mammographically detected DCIS, the present study was undertaken to determine the outcome of treatment of nonpalpable, mammographically detected intraductal carcinoma of the breast using breast-conserving surgery and definitive breast irradiation., Materials and Methods: An analysis was performed of 110 women who presented with unilateral, nonpalpable, mammographically detected intraductal carcinoma of the breast and who were treated with breast-conserving surgery and definitive breast irradiation at 10 institutions in Europe and the United States. In all patients, complete gross excision of the primary tumor was performed, and breast irradiation was delivered with definitive intent. When performed, pathologic axillary lymph node staging was node negative (n=29). The median follow-up time was 9.3 years., Results: The 10-year actuarial overall survival rate was 93%, and the 10-year actuarial cause-specific survival rate was 96%. The 10-year actuarial rate of freedom from distant metastases was 96%. There were 15 local recurrences in the treated breast. The actuarial rate of local failure was 7% at 5 years and 14% at 10 years. The histology of the local recurrence was intraductal carcinoma in 9 cases and invasive ductal carcinoma (with or without associated intraductal carcinoma) in 6 cases. The median time to local recurrence was 5.0 years (mean, 5.4; range, 2.1-15.2). With a median follow-up time of 4.4 years after salvage treatment, 14 of the 15 patients with local recurrence were alive without evidence of disease at the time of last follow-up examination. The crude incidence of local recurrence was 7% (3/42) when the final pathology margin of tumor excision was negative, 29% (5/17) when the margin was close or positive, and 14% (7/51) when the margin was unknown. There was no difference in the rate of local recurrence based on pathologic characteristics of the primary tumor., Discussion: Results from the present study demonstrate high rates of overall survival, cause-specific survival, and freedom from distant metastases at 10 years following the treatment of nonpalpable, mammographically detected DCIS of the breast using breast-conserving surgery and definitive breast irradiation. Local recurrences within the treated breast were detected early and were treated with salvage for cure. These results support the initial treatment of nonpalpable, mammographically detected DCIS of the breast using breast-conserving surgery and definitive breast irradiation. Improvements in patient selection have the potential to reduce the risk of local recurrence.

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.

Background: Breast-conserving therapy followed by adjuvant radiotherapy represents an alternative to mastectomy as a treatment for invasive breast cancer. When excisional biopsy has been performed outside the parent institution, reexcision is often performed, with tumor being identified in 32% to 62% of the subsequent specimens. We analyzed not only the factors associated with a positive reexcision but also those factors associated with final surgical margins that are positive for tumor., Methods: Between 1978 and 1991, 956 female patients with American Joint Committee on Cancer clinical stage I or II breast cancer were treated with breast-conserving therapy where a total of 420 patients underwent reexcision after an initial excisional biopsy. Several factors were analyzed to determine their association with a positive reexcision, the status of the final surgical margin, and the nature of the disease present within the reexcision specimen., Results: Factors that correlated with a positive reexcision in both univariate and multivariate analysis were clinical tumor size, method of detection, the pathologic status of the axillary lymph nodes, and the histologic appearance. Those factors associated with finding invasive disease at the time of reexcision were clinical tumor size, clinical presentation, and nodal status. The single factor associated with finding residual in situ disease at the time of reexcision was histologic appearance of the primary tumor. A final positive margin was associated with method of tumor detection, age of the patient, and the presence of axillary lymph node metastases., Conclusions: The most significant factors associated with a positive reexcision are clinical tumor size, method of tumor detection, pathologic nodal status, and histologic appearance. Patients with larger tumors or those that are detected by physical examination, as well as invasive lobular carcinomas, may require a more generous initial resection to achieve negative surgical margins and avoid the likelihood of reexcision.

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.

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.

Purpose: To assess the impact of young age on outcome in women with early stage breast cancer undergoing conservative surgery and radiation., Methods and Materials: Between 1981 and 1991, 980 patients with Stage I and II breast cancer underwent excisional biopsy, axillary dissection, and radiation. The median follow-up was 4.6 years, with a range of 1 month to 11 years. The patients were divided into three groups, based on age at the time of diagnosis: (a) age < or = 35 years--64 patients, (b) age 36-50 years--363 patients, and (c) age > 50 years--553 patients. The comparability of the groups was assessed in terms of clinical factors (tumor size and race), histopathologic factors (histologic subtype, final resection margin, estrogen and progesterone receptor status, pathologic nodal status), and treatment related factors (reexcision, median total dose to the primary, region(s) treated with radiation, and the use of adjuvant systemic chemotherapy and/or tamoxifen). Outcome was evaluated for overall, relapse-free, and cause-specific survival and patterns of first failure (breast, regional nodes, and distant metastasis)., Results: There were no significant differences among the three groups in terms of race, clinical tumor size, pathology of the primary tumor, pathologic nodal status, final margin of resection, progesterone receptor status, median total dose to the primary tumor, or the regions treated. However, younger women were significantly more likely to have estrogen receptor negative tumors, undergo reexcision, and receive adjuvant systemic chemotherapy without tamoxifen. Younger women were found to have a statistically significantly decreased 8-year actuarial relapse-free survival (53% vs. 67% vs. 74%, p = 0.009), cause-specific survival (73% vs. 84% vs. 90%, p = 0.02), freedom from distant metastasis (76% vs. 75% vs. 83%, p = 0.02), and a significantly increased risk of breast recurrence (24% vs. 14% vs. 12%, p = 0.001), and regional node recurrence (7% vs. 1% vs. 1%, p = 0.0002). The patients were further divided on the basis of their pathologic nodal status. There were no statistically significant differences among the three age groups for axillary node-positive patients for overall survival (75% vs. 80% vs. 74%), relapse-free survival (73% vs. 73% vs. 62%), cause-specific survival (76% vs. 85% vs. 80%), and freedom from distant metastasis (75% vs. 75% vs. 72%), or breast recurrence (0% vs. 9% vs. 6%). The findings were identical when the analysis was restricted to node-positive patients who received chemotherapy. However, for axillary node-negative women, young age was associated with a statistically significant decreased overall survival (71% vs. 83% vs. 92%), relapse-free survival (51% vs. 65% vs. 76%), cause-specific survival (71% vs. 86% vs. 93%), freedom from distant metastasis (77% vs. 76% vs. 88%), and a statistically significant increased risk of breast recurrence (40% vs. 16% vs. 13%), and regional node recurrence (3% vs. 1% vs. 0%). The risk of a breast recurrence in axillary node-negative young women was decreased by the addition of adjuvant systemic chemotherapy but not by the use of reexcision., Conclusions: The present analysis demonstrates that young women with early stage breast cancer do significantly worse when compared to older women in terms of relapse-free survival, cause-specific survival, distant metastasis and breast and regional node recurrence. However, the adverse effect of young age on outcome appears to be limited to the node-negative patients. These findings suggest that node-negative early stage breast cancer in young women is a more aggressive disease, with an increased risk for all patterns of failure and a decreased survival.

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.

To develop and optimize algorithms for the identification of newly diagnosed and treated cases of women with carcinoma of the breast, an analysis was performed of cases identified from the claims database of a large health maintenance organization (U.S. Healthcare). An initial algorithm was developed from the patterns of claims which suggested common clinical presentations of carcinoma of the breast, and the positive predictive value was 88% (411/469). To attempt to improve upon the positive predictive value, multiple modifications of the initial algorithm were performed. The best identified modification of the initial algorithm yielded a positive predictive value of 93% (400/432) with a loss of only 3% (11/411) of the true positive cases. These results demonstrate that logic-based algorithms can be used as a valid and efficient method of identifying large numbers of cases from claims data with specific clinical characteristics. The best algorithm identified provides a powerful and accurate tool to perform health care analysis and research on large populations of women with newly diagnosed and treated carcinoma of the breast.

Increased total antigen amounts of cathepsin D in breast tissue have been reported to be associated with increased disease recurrence, more frequent metastasis, and increased mortality in breast cancer patients. In the present study, Western blotting analysis has been used for the first time to determine the relative amounts of precursor and processed forms of cathepsin D in sera and breast tissue of patients with breast cancer, benign breast disease, and normal controls. Sera gave similar blots for breast cancer patients and controls with two major forms of cathepsin D (M(r) 52,000 and 27,000). Malignant breast tissue contained the two forms of cathepsin D found in sera and an additional M(r) 31,000 form which was found in significantly increased (P < 0.001) relative amounts in breast tissue from 43 breast cancer patients [24 +/- 12% (SD)] when compared to 51 benign breast disease patients (13 +/- 8.9%) and 23 normal controls (1.8 +/- 4.4%). Preliminary analysis of subgroups of benign breast disease patients suggested no significant difference (P = 0.41) in relative amounts of the M(r) 31,000 form of cathepsin D between proliferative-type and non-proliferative-type fibrocystic breast disease. A cathepsin D assay has been optimized for human breast tissue and used to demonstrate for the first time significantly increased (P < 0.001) amounts of pepstatin-inhibitable, cathepsin D-specific activity in breast tissue from 36 breast cancer patients (2.2 +/- 1.4 units/mg of protein) when compared to 47 benign breast disease patients (0.63 +/- 0.43) and 23 normal controls (0.24 +/- 0.21). Preliminary analysis of subgroups of benign breast disease patients suggested no significant difference (P = 0.21) in pepstatin-inhibitable, cathepsin D-specific activity between proliferative-type and nonproliferative-type fibrocystic breast disease. The positive correlation (r = 0.82) of increased amounts of the M(r) 31,000 form of cathepsin D and increased pepstatin-inhibitable, cathepsin D enzymatic activity in malignant breast tissue suggests that the M(r) 31,000 form is the proteolytically active form of the enzyme which may be involved in the development and/or metastatic spread of breast cancer.

Purpose: Women with Stage I-II invasive breast cancer who present with gross multicentric disease or diffuse microcalcifications have a significant risk of breast recurrence when treated with conservative surgery and radiation. The purpose of this report is to present the results of mastectomy in this group of patients., Methods and Materials: Between 1982 and 1989, 88 patients with clinical Stage I-II breast cancer who presented with clinical and mammographic evidence of gross multicentric disease or diffuse microcalcifications underwent modified radical mastectomy. Median followup was 4 years for the 57 patients with gross multicentric disease and 5.6 years for 31 patients with diffuse microcalcifications. At the time of mastectomy, 42% of patients were found to have positive axillary nodes. Following mastectomy, 15 patients received post mastectomy radiation and 35 patients received adjuvant systemic chemotherapy., Results: When compared to a group of 1295 patients with unifocal, Stage I-II breast cancer, treated with conservative surgery and radiation during the same time period, patients with gross multicentric disease and diffuse microcalcifications had a significantly higher incidence of > or = 4 positive nodes, patients with gross multicentric disease had a lower incidence of positive resection margins following mastectomy and patients with diffuse microcalcifications were younger. The 5-year actuarial risk of an isolated local-regional recurrence was 8% for patients with gross multicentric disease or diffuse microcalcifications and 7% for patients with unifocal disease. Patients with gross multicentric disease or diffuse microcalcifications and > or = 4 positive axillary nodes who did not receive post mastectomy radiation had an increased risk for local regional recurrence. There were no significant differences in the 5-year actuarial overall or relapse-free survival (88% and 73% gross multicentric disease, 97% and 86% diffuse microcalcifications and 90% and 79% unifocal disease), freedom from distant metastasis (76% gross multicentric disease, 90% diffuse microcalcifications, 86% unifocal disease) or incidence of contralateral breast cancer (10% gross multicentric disease, 13% diffuse microcalcifications, 8% unifocal disease) among the three groups., Conclusion: The present study demonstrates no increased risk of local-regional recurrence in patients with gross multicentric disease or diffuse microcalcifications undergoing mastectomy in contrast to the increased risk of breast recurrence in patients with gross multicentric disease undergoing conservative surgery and radiation. Indications for post mastectomy radiation include > or = 4 positive nodes or close or positive surgical margins. Despite a significantly higher incidence of > or = 4 positive nodes, patients with gross multicentric disease and diffuse microcalcifications have a 5-year actuarial overall and relapse-free survival comparable to a group of patients with unifocal disease treated with conservative surgery and radiation.

The prognostic implications of detection mode in local recurrence after lumpectomy and radiation therapy were assessed. Seventy-two women treated with lumpectomy and irradiation for American Joint Committee on Cancer stages I and II invasive breast cancer developed recurrent cancer in the ipsilateral breast, had physical examination and mammography performed at the time of recurrence, and underwent salvage mastectomy. There was a statistically significant association between detection with mammography alone and lower T stage (P = .05), and there was a nonstatistically significant trend toward noninvasive histologic findings. No significant association was noted between detection method and site of recurrent current cancer in the breast, interval to recurrence, or patient age. There were nonstatistically significant trends toward improved relapse-free survival and overall survival for patients with recurrences detected solely with mammography. that postirradiation surveillance mammography is important for the early detection of recurrent cancer. While the trend did not reach statistical significance, detection with mammography alone had a clinically apparent impact on relapse-free and overall survival.

Background: To evaluate the pathologic characteristics of the primary tumor relative to local control, survival, and freedom from distant metastases, an analysis was performed of 172 patients with ductal carcinoma in situ (intraductal carcinoma) of the breast treated with breast-conserving surgery and definitive breast irradiation., Methods: The clinical records and pathology slides were reviewed from 172 women with ductal carcinoma in situ treated with breast-conserving surgery and definitive breast irradiation at multiple institutions in Europe and the United States. Central pathology review was performed by one pathologist without knowledge of the clinical outcome. The clinical outcome was measured in terms of local control, overall survival, cause-specific survival, and freedom from distant metastases. The median follow-up time was 84 months (range, 17-177 months)., Results: The pathologic parameters evaluated were histologic subtype, nuclear grade, amount of necrosis, and final pathology margin. The only pathologic parameter that correlated with the rate of local recurrence was the presence versus the absence of the combination of the histologic subtype of comedo carcinoma plus nuclear grade 3 (8-year actuarial rate of local recurrence of 20% versus 5%, respectively; P = 0.009 on univariate analysis; P = 0.017 on multivariate analysis). None of the pathologic parameters evaluated correlated with overall survival (all P > or = 0.16), cause-specific survival (all P > or = 0.13), or freedom from distant metastases (all P > or = 0.13)., Conclusions: These results have demonstrated that there are important differences in the rate of local recurrence based on the pathologic characteristics of the primary tumor for women with ductal carcinoma in situ treated with breast-conserving surgery and definitive irradiation. However, the differences in local recurrence have not been associated with differences in survival or freedom from distant metastases. Careful follow-up for patients at increased risk for local recurrence is warranted because of the potential ability to salvage patients with local recurrence.

Apocrine features occurring in sclerosing adenosis (apocrine adenosis), atypical ductal hyperplasia (ADH), and non-comedo ductal carcinoma in situ (DCIS) often add to diagnostic difficulty. We have evaluated the usefulness of DNA content determined by image analysis in apocrine metaplasia and hyperplasia, apocrine adenosis, ADH, DCIS, lobular carcinoma in situ, invasive ductal carcinoma, and infiltrating lobular carcinoma as a potential diagnostic aid in some of these problematic breast lesions with apocrine features. Infiltrating ductal carcinoma and DCIS were further subdivided into high- or low-grade category based on nuclear features. Microscopic fields containing 63 lesions were identified in slides from breast excisions. From each selected area 100 cells in corresponding fields in paired Feulgen-stained sections were digitized for computerized ploidy analysis with lymphocyte nuclei in the same slides serving as internal diploid controls. Aneuploidy was assessed using combined DNA index and modified Auer histogram criteria for DNA content abnormalities. There was strong association between the assessment of nuclear grade and ploidy (Fisher's exact test, P < .00001). All but one of the benign and low-grade malignant lesions (97%) were in the diploid range (six of seven apocrine metaplasia cases, three of three apocrine adenosis cases, 14 of 14 ADH cases, 10 of 10 low-grade DCIS cases, two of two lobular carcinoma in situ cases, and two of two infiltrating lobular carcinoma cases). In contrast, 24 of 25 (96%) of the high-grade malignant lesions were aneuploid (10 of 10 DCIS cases and 14 of 15 infiltrating ductal carcinoma cases). We conclude that DNA ploidy status does not offer additional diagnostic information to light microscopy in distinguishing among benign apocrine proliferations, ADH, and low-grade DCIS since these proliferations share a diploid range DNA content.

Between 1977 and 1986, 75 black and 615 white women with American Joint Committee (AJC) Stages I and II breast cancer were treated with excisional biopsy, axillary dissection, and radiation therapy for breast conservation. Cyclophosphamide, methotrexate, and 5-fluorouracil, with and without prednisone and tamoxifen, was given to 92% of premenopausal, 83% of perimenopausal, and 63% of postmenopausal node-positive women; 20 of 106 (19%) postmenopausal node-positive women received tamoxifen only. The clinical characteristics of the similarly treated patients were compared. The 5-year actuarial local only first failure rate was 5% for black women and 6% for white women (P = 0.53). Regional only failure as the first site of failure was 9% for blacks versus 1% for whites (P = 0.002), with regional recurrence as any component of first failure being 16% for blacks and 4% for whites (P = 0.001). The supraclavicular fossa was identified as the primary site of regional recurrence in black patients with either pathologically positive or negative axillae. Distant metastases as the only site of first failure were significantly greater in the black population with a 20% 5-year actuarial failure rate versus 11% in white patients (P = 0.01). The 5-year actuarial overall survival for the black patients was 82% versus 91% for the white patients (P = 0.01), with no-evidence-of-disease (NED) survival being 64% and 83% (P = 0.0002) and relapse-free survival (RFS) being 61% and 77% (P = 0.01), respectively. Black patients younger than 40 years of age or with pathologically positive axillary nodes had significantly worse NED, RFS, and overall survival compared with similarly staged white patients. Cosmetic results were analyzed at 3 and 5 years after completion of therapy. Although significantly fewer black patients had an excellent-to-good cosmetic result at 3 years compared with white patients, the results were not significantly different at 5 years. These results show that appropriately selected black patients with early stage breast cancer have excellent local control after conservative surgery and radiation therapy and should continue to be offered breast preservation as an alternative to mastectomy. Patterns of failure, however, demonstrated higher regional and distant recurrence rates and lower NED, RFS, and overall survival rates in most subsets of black patients reviewed.

Using the CAS-200 image analysis system, we compared the relationship between semiautomated computer measurements (QIC score) and visual scoring (H score) on 30 breast cancer fine needle aspirates (FNAs) and corresponding tissue specimens stained by the estrogen receptor immunocytochemical assay. These results were compared to the corresponding biochemistry assays for ER. We also investigated whether the computerized system could decrease false-negative staining for ER in 32 cryostat sections. QIC scores were generated using fixed nuclear and antibody thresholds after standardizing the illumination. Computer quantitation was essentially as precise as visual semiquantitation for FNAs: a small but significant correlation was found between tumor ER content and QIC score (r = .504, P less than .02) as compared with H score and ER content (rs = .55, P less than .005). The computerized system did not decrease the false-negative rate in cryostat sections. In all, computerized quantitation was no better than visual analysis of ER staining in these breast carcinomas.

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)

Between 1977 and 1986, 879 patients with Stage I and II breast cancer underwent excisional biopsy, axillary dissection, and radiation. Median follow-up was 61 months (range 2-159 months). The patients were divided into seven groups based on histologic subtype: (a) 368 patients with both infiltrating and intraductal ductal carcinoma, (b) 389 infiltrating ductal carcinoma, (c) 41 infiltrating lobular carcinoma, (d) 23 combined infiltrating ductal and lobular carcinoma, (e) 28 medullary carcinoma, (f) 12 colloid carcinomas, and (g) 18 tubular carcinomas. Significant differences in clinical T status, pathologic nodal involvement, administration of chemotherapy, estrogen receptor positivity, progesterone receptor positivity, and age were observed between some histologic subgroups. Tubular and colloid carcinomas were more likely to present with T1 lesions, hormone receptor positivity, and node negative status than the other histologic subtypes. Most medullary carcinomas were hormone receptor negative and were younger than 50 years old. Infiltrating lobular carcinoma patients were more frequently lymph node negative, older, node negative, and estrogen receptor positive compared to the other groups (except for tubular and colloid patients). Differences in the administration of chemotherapy primarily reflected differences in lymph node involvement. Location of the tumor in the breast and menopausal status did not correlate with histologic subtype. There were no significant differences in 5-year actuarial overall survival, cause-specific survival, or relapse-free survival between the histologic categories. In addition, patterns of first failure were not significantly different among the histologic groups in terms of local-only first failure, any local component of first failure, regional-only first failure, or any regional component of first failure. There was, however, a difference among the seven groups in distant metastasis-only at first failure with invasive ductal carcinomas having the highest rate. Despite this difference, histologic subtype had no impact on survival. The site of in-breast failure relative to the location of the original tumor was not significantly different between groups. The histologic subtype of invasive breast cancer is not an independent risk factor in predicting survival or pattern of failure. Conservative surgery and radiation therapy is effective treatment of ductal, lobular, medullary, colloid, and tubular invasive breast cancer.

An analysis was performed of 39 consecutive women with microinvasive ductal carcinoma of the breast treated with breast-conserving surgery and definitive irradiation during the period 1977 to 1988. Microinvasive ductal carcinoma was defined as predominantly intraductal carcinoma with microscopic or early invasion. Surgical treatment of the primary tumor included excisional biopsy or wide resection. Axillary lymph node staging showed that 37 patients were pathologically node negative and two patients were pathologically node positive, each with only one positive lymph node. The median follow-up was 55 months (mean = 65 months; range = 25-135 months). The 5-year actuarial rate of overall and cause-specific survival were both 97%. The 5-year actuarial rate of freedom from distant metastases was 93%. Nine patients developed a recurrence in the breast; eight of the nine patients had isolated local only first failures, and one of the nine patients had a local recurrence simultaneously with distant metastases. The median time to local failure was 42 months (mean = 53 months; range = 20-116 months). Of the eight patients with local only first failure, seven patients have been salvaged with further treatment and remain free of disease at the time of last follow-up, and one patient has died of subsequent distant metastatic disease. Median follow-up after salvage treatment was 29 months (mean = 27 months; range = 0-54 months). Comparison of the patients with microinvasive ductal carcinoma with two control groups of intraductal carcinoma and invasive ductal carcinoma was performed. Although the rate of local failure was significantly higher for patients with microinvasive ductal carcinoma as compared to the two control groups, the rates of survival and freedom from distant metastases for patients with microinvasive ductal carcinoma were intermediate to the two control groups. Because of the high rates of survival and freedom from distant metastases and because of the ability to salvage patients with local recurrence, breast-conserving surgery and definitive irradiation should continue to be considered as an alternative to mastectomy for appropriately selected and staged patients with microinvasive ductal carcinoma of the breast.

An analysis of 259 women with 261 treated breasts from nine institutions in Europe and the United States was performed to determine the 10-year results of the treatment of intraductal carcinoma of the breast with definitive irradiation. All patients had undergone complete gross excision of the primary intraductal carcinoma, and definitive breast irradiation was delivered in all cases. The median follow-up time was 78 months (range, 11 to 197 months). The 10-year actuarial overall survival rate was 94%, and the 10-year actuarial cause-specific survival rate (including deaths only from carcinoma of the breast) was 97%. The 10-year actuarial rate of freedom from distant metastases was 96%. There were 28 failures in the breast, and the 10-year actuarial rate of local failure was 16%. The pathologic type of local recurrences showed invasive ductal carcinoma in 14 of 28 recurrences (50%) and noninvasive ductal carcinoma in 14 of 28 recurrences (50%). The median time to local failure was 50 months (range, 17 to 129 months). Twenty-four of 28 patients with local failure were salvaged with additional treatment, generally mastectomy, and 4 of 28 patients with local failure subsequently had distant metastases. Median follow-up time after salvage treatment of breast recurrence was 29 months (range, 3 to 90 months). Two patients without local failure subsequently had distant metastases, one of which occurred after a node-positive, contralateral breast carcinoma. These results demonstrate high rates of overall survival, cause-specific survival, and freedom from distant metastases for the treatment of patients with intraductal carcinoma of the breast. The local recurrences within the treated breast were generally salvaged with additional treatment, although with limited follow-up. Because of the long natural history of intraductal carcinoma of the breast, prolonged and careful follow-up of patients after breast-conservation and definitive irradiation is required.

To evaluate the significance of the pathology margins of the tumor excision on the outcome of treatment, an analysis was performed of 697 consecutive women with clinical Stage I or II invasive carcinoma of the breast treated with breast-conserving surgery and definitive irradiation. Complete gross excision of the primary tumor was performed in all cases, and an axillary staging procedure was performed to determine pathologic axillary lymph node status. The 697 patients were divided into four groups based on the final pathology margin from the primary tumor excision or from the re-excision if performed. These four groups were: (a) 257 patients with a negative margin (greater than 2 mm), (b) 57 patients with a positive margin, (c) 37 patients with a close margin (less than or equal to 2 mm), and (d) 346 patients with an unknown margin. The patients with positive final pathology margins were focally positive on microscopic examination. Patients with grossly positive margins or with diffusely positive microscopic margins were treated with conversion to mastectomy. There was a significant difference in the total radiation dose for the four groups (median dose of 6000 vs 6500 vs 6400 vs 6240 cGy, respectively; p less than .0001). There was no significant difference among the four groups for 5-year actuarial overall survival (p = .19), no evidence of disease (NED) survival (p = .95), or relapse-free survival (p = .80). There was no significant difference among the four groups for five year actuarial local or regional control (all p greater than or equal to .29). Subset analyses did not identify any poor outcome subgroups. These results have demonstrated that selected patients with focally positive or close microscopic pathology margins can be adequately treated with definitive breast irradiation. Patient selection and the technical delivery of radiation treatment including a boost may have been important contributing factors to the good outcome in these patients.

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.

Between 1967 and 1988 128 patients with isolated local-regional recurrence of breast cancer after mastectomy were treated with definitive radiation therapy. Recurrence was confined to a single site in 108 patients and multiple sites in 20. The chest wall was the most common location (86) and the supraclavicular region was the second most common (20). Surgical treatment for recurrence prior to irradiation consisted of excision of all gross disease in 78 patients and incisional biopsy in 49 patients. Irradiation was directed to the entire chest wall in 19% of patients with isolated chest wall recurrences and to the chest wall and regional nodes in 81%. In patients with isolated nodal failures, treatment was directed to the nodal site and chest wall in 87% and to the regional site alone in 13%. Patients with multiple sites received treatment to the chest wall and regional nodes in all cases. Electively treated sites usually received 4500-5000 cGy. Following excision of chest wall disease, the median dose was 6000 cGy. Gross disease on the chest wall received a median dose of 6100 cGy. Gross disease in nodal sites received a median dose of 5600 cGy; 66 patients received systemic therapy at recurrence. The 5-year actuarial local-regional control was 43%. In a multivariate analysis only the estrogen receptor status of the recurrence remained significant (p = .002). The 5-year actuarial survival was 49% with a relapse-free survival of 24%. In a multivariate analysis for survival, the disease-free interval (p = .007), local regional control (p = .006), and excisional biopsy for recurrence (p = .03) remained significant. In a multivariate analysis for relapse-free survival, the disease-free interval (p = .03), excisional biopsy (p = .0001), and the extent of axillary nodal involvement (p = .007) remained significant. In the subgroup of patients with a disease-free interval greater than or equal to 24 months, excisional biopsy, and local regional control, the 5-year survival was 61% with a relapse-free survival of 59%. This subgroup represents 18% of the entire group and has a relatively good prognosis after recurrence.