Atypical ductal hyperplasia in men with gynecomastia: what is their breast cancer risk?

PURPOSE: Atypical ductal hyperplasia (ADH) significantly increases the risk of breast cancer in women. However, little is known about the implications of ADH in men. METHODS: Review of 932 males with breast pathology was performed to identify cases of ADH. Patients were excluded if ADH was upgraded to cancer on excision, or if they had contralateral breast cancer. Cases were reviewed to determine whether any male with ADH developed breast cancer. RESULTS: Nineteen males were diagnosed with ADH from June 2003 to September 2018. All had gynecomastia. Surgical procedure was mastectomy in 8 patients and excision/reduction in 11. One patient had their nipple areola complex removed, and 1 required a free nipple graft. Median patient age at ADH diagnosis was 25 years (range 18-72 years). Of the 14 patients with bilateral gynecomastia, 10 had bilateral ADH and 4 had unilateral. Five cases of ADH were described as severe, bordering on ductal carcinoma in situ. No patient reported a family history of breast cancer. No patient took tamoxifen. At a mean follow-up of 75 months (range 4-185 months), no patient developed breast cancer. CONCLUSION: Our study is the first to provide follow-up information for males with ADH. With 6 years of mean follow-up, no male in our series has developed breast cancer. This suggests that either ADH in men does not pose the same risk as ADH in women or that surgical excision of symptomatic gynecomastia in men effectively reduces the risk of breast cancer.

Incidental breast carcinoma: incidence, management, and outcomes in 4804 bilateral reduction mammoplasties.

INTRODUCTION: Bilateral reduction mammoplasty is one of the most common plastic surgery procedures performed in the U.S. This study examines the incidence, management, and prognosis of incidental breast cancer identified in reduction specimens from a large cohort of reduction mammoplasty patients. METHODS: Breast pathology reports were retrospectively reviewed for evidence of incidental cancers in bilateral reduction mammoplasty specimens from five institutions between 1990 and 2017. RESULTS: A total of 4804 women met the inclusion criteria of this study; incidental cancer was identified in 45 breasts of 39 (0.8%) patients. Six patients (15%) had bilateral cancer. Overall, the maximum diagnosis by breast was 16 invasive cancers and 29 ductal carcinomas in situs. Thirty-three patients had unilateral cancer, 15 (45.5%) of which had high-risk lesions in the contralateral breast. Twenty-one patients underwent mastectomy (12 bilateral and nine unilateral), residual cancer was found in 10 in 25 (40%) therapeutic mastectomies. Seven patients did not undergo mastectomy received breast radiation. The median follow-up was 92 months. No local recurrences were observed in the patients undergoing mastectomy or radiation. Three of 11 (27%) patients who did not undergo mastectomy or radiation developed a local recurrence. The overall survival rate was 87.2% and disease-free survival was 82.1%. CONCLUSIONS: Patients undergoing reduction mammoplasty for macromastia have a small but definite risk of incidental breast cancer. The high rate of bilateral cancer, contralateral high-risk lesions, and residual disease at mastectomy mandates thorough pathologic evaluation and careful follow-up of these patients. Mastectomy or breast radiation is recommended for local control given the high likelihood of local recurrence without either.

Discrepancy in risk assessment of hormone receptor positive early-stage breast cancer patients using breast cancer index and recurrence score.

PURPOSE: A recent comparison of the prognostic accuracy of Breast Cancer Index (BCI) and the Recurrence Score (RS) showed that BCI was more precise than RS. BCI identified a subset of RS low and intermediate risk patients with clinically relevant elevated rates of distant recurrences (DR). The current study analyzed the correlation of BCI and RS risk classification to clinical and pathological parameters and further examined the re-categorization between the two risk group indices in a multi-institutional cohort of hormone receptor positive (HR+) breast cancer patients. METHODS: 560 women with HR+, lymph node-negative breast cancer who underwent testing with RS as part of their routine clinical care were included in the final analysis. Individual risk was assessed using predefined categories of RS and BCI (Low, Intermediate and High, respectively). Correlations between BCI, RS, and standard clinical-pathological prognostic factors were examined, and re-categorization of risk groups between BCI and RS was analyzed. RESULTS: An overall significant association between histological tumor grade and RS or BCI was observed with high-grade tumors more prevalent among RS and BCI high-risk patients. The invasive ductal carcinoma histologic subtype was associated with 98% and 93% of high-risk RS and BCI cases, respectively. The invasive lobular subtype accounted for 0% and 6% of high-risk RS and BCI cases, respectively. A poor agreement between the two biomarker risk group indices was demonstrated with more than 51% of the total cohort stratified differently between BCI and RS. As compared with RS, BCI stratified fewer patients into the intermediate-risk group (29% vs. 39%, BCI and RS, respectively) and more patients into the high-risk group (19% vs. 7%, BCI and RS, respectively). Subsets of both RS low- and intermediate-risk patients were identified by BCI as high risk. CONCLUSIONS: In this clinical series, BCI and RS risk groups demonstrated a significant association with histological tumor grade. BCI showed a modest correlation with tumor size and no correlation with age, while RS showed no correlation with tumor size or age. Compared with RS, BCI classifies fewer intermediate risk patients, identifies subsets of low and intermediate RS risk patients as high-risk, and provides distinct individualized risk assessment for patients with early-stage breast cancer.

Pathologic findings in reduction mammoplasty specimens: a surrogate for the population prevalence of breast cancer and high-risk lesions.

PURPOSE: Mammoplasty removes random samples of breast tissue from asymptomatic women providing a unique method for evaluating background prevalence of breast pathology in normal population. Our goal was to identify the rate of atypical breast lesions and cancers in women of various ages in the largest mammoplasty cohort reported to date. METHODS: We analyzed pathologic reports from patients undergoing bilateral mammoplasty, using natural language processing algorithm, verified by human review. Patients with a prior history of breast cancer or atypia were excluded. RESULTS: A total of 4775 patients were deemed eligible. Median age was 40 (range 13-86) and was higher in patients with any incidental finding compared to patients with normal reports (52 vs. 39 years, p = 0.0001). Pathological findings were detected in 7.06% (337) of procedures. Benign high-risk lesions were found in 299 patients (6.26%). Invasive carcinoma and ductal carcinoma in situ were detected in 15 (0.31%) and 23 (0.48%) patients, respectively. The rate of atypias and cancers increased with age. CONCLUSION: The overall rate of abnormal findings in asymptomatic patients undergoing mammoplasty was 7.06%, increasing with age. As these results are based on random sample of breast tissue, they likely underestimate the prevalence of abnormal findings in asymptomatic women.

Reassessing risk models for atypical hyperplasia: age may not matter.

PURPOSE: The aim of this study was to investigate the influence of age at diagnosis of atypical hyperplasia ("atypia", ductal [ADH], lobular [ALH], or severe ADH) on the risk of developing subsequent invasive breast cancer or ductal carcinoma in situ (DCIS). METHODS: Using standard survival analysis methods, we retrospectively analyzed 1353 women not treated with chemoprevention among a cohort of 2370 women diagnosed with atypical hyperplasia to determine the risk relationship between age at diagnosis and subsequent breast cancer. RESULTS: For all atypia diagnoses combined, our cohort showed a 5-, 10-, and 15-year risk of invasive breast cancer or DCIS of 0.56, 1.25, and 1.30, respectively, with no significant difference in the (65,75] year age group. For women aged (35,75] years, we observed no significant difference in the 15-year risk of invasive breast cancer or DCIS after atypical hyperplasia, although the baseline risk for a 40-year-old woman is approximately 1/8 the risk of a 70-year-old woman. The risks associated with invasive breast cancer or DCIS for women in our cohort diagnosed with ADH, severe ADH, or ALH, regardless of age, were 7.6% (95% CI 5.9-9.3%) at 5 years, 25.1% (20.7-29.2%) at 10 years, and 40.1% (32.8-46.6%) at 15 years. CONCLUSION: In contrast to current risk prediction models (e.g., Gail, Tyrer-Cuzick) which assume that the risk of developing breast cancer increases in relation to age at diagnosis of atypia, we found the 15-year cancer risk in our cohort was not significantly different for women between the ages of 35 (excluded) and 75. This implies that the "hits" received by the breast tissue along the "high-risk pathway" to cancer might possibly supersede other factors such as age.

Using machine learning to parse breast pathology reports.

PURPOSE: Extracting information from electronic medical record is a time-consuming and expensive process when done manually. Rule-based and machine learning techniques are two approaches to solving this problem. In this study, we trained a machine learning model on pathology reports to extract pertinent tumor characteristics, which enabled us to create a large database of attribute searchable pathology reports. This database can be used to identify cohorts of patients with characteristics of interest. METHODS: We collected a total of 91,505 breast pathology reports from three Partners hospitals: Massachusetts General Hospital, Brigham and Women's Hospital, and Newton-Wellesley Hospital, covering the period from 1978 to 2016. We trained our system with annotations from two datasets, consisting of 6295 and 10,841 manually annotated reports. The system extracts 20 separate categories of information, including atypia types and various tumor characteristics such as receptors. We also report a learning curve analysis to show how much annotation our model needs to perform reasonably. RESULTS: The model accuracy was tested on 500 reports that did not overlap with the training set. The model achieved accuracy of 90% for correctly parsing all carcinoma and atypia categories for a given patient. The average accuracy for individual categories was 97%. Using this classifier, we created a database of 91,505 parsed pathology reports. CONCLUSIONS: Our learning curve analysis shows that the model can achieve reasonable results even when trained on a few annotations. We developed a user-friendly interface to the database that allows physicians to easily identify patients with target characteristics and export the matching cohort. This model has the potential to reduce the effort required for analyzing large amounts of data from medical records, and to minimize the cost and time required to glean scientific insight from these data.

Breast Cancer Risk and Follow-up Recommendations for Young Women Diagnosed with Atypical Hyperplasia and Lobular Carcinoma In Situ (LCIS).

BACKGROUND: The risk of breast cancer in young women diagnosed with atypical hyperplasia and (LCIS) is not well defined. The objectives were to evaluate outcomes and to help determine guidelines for follow-up in this population. METHODS: A retrospective review of women under age 35 diagnosed with ADH, ALH, LCIS, and severe ADH from 1987 to 2010 was performed. Patient characteristics, pathology and follow-up were determined from chart review. RESULTS: We identified 58 young women with atypical breast lesions. Median age at diagnosis was 31 years (range 19-34). 34 patients had ADH, 11 had ALH, 8 had LCIS, and 5 had severe ADH. 7 (12%) patients developed breast cancer. The median follow-up was 86 months (range 1-298). Median time to cancer diagnosis was 90 months (range 37-231). 4 cancers were on the same side, 3 were contralateral. 4 were IDC, 1 was ILC, and 2 were DCIS. Cancer was detected by screening mammogram in 4 patients, 2 by clinical exam, and 1 unknown. In the entire cohort, 26 (45%) patients had screening mammograms as part of their follow up, 12 patients had only clinical follow up, and 20 had no additional follow up. 13 patients required subsequent biopsies. CONCLUSION: Young women with atypical breast lesions are at a markedly increased risk for developing breast cancer and should be followed closely. Based on our findings, we recommend close clinical follow-up, MRI starting at age 25 through age 29, and screening mammograms for those over 30 in this high-risk group of patients.

Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor 2 Expression Rates in Invasive Breast Carcinoma: A Study of 21 Institutions.

CONTEXT.­: Laboratories performing predictive marker testing for breast carcinoma are encouraged to compare patient results to published benchmarks. OBJECTIVE.­: To collect expression rates for estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) in invasive breast carcinoma from multiple laboratories. DESIGN.­: Participants submitted data from up to 50 primary cases during the study period. Participants reported ER, PgR, and HER2 results in addition to demographic and histologic information. Participants also provided annual institution-level expression rates. RESULTS.­: A total of 21 institutions submitted data for 687 cases. Aggregate positivity rates for ER and PgR were 85.6% and 75.1%, respectively. Receptor positivity rates were higher in well-differentiated (grade 1) tumors (ER, 97.4%; PgR, 88.0%) compared with moderately differentiated (grade 2) tumors (ER, 92.4%; PgR, 84.0%) and poorly differentiated (grade 3) tumors (ER, 61.8%; PgR, 48.0%). Expression rates were higher in postmenopausal women (ER, 87.2%) than premenopausal women (ER, 79.6%) and higher in lobular carcinomas (ER, 98.7%; PgR, 85.3%) than ductal carcinomas (ER, 84.1%; PgR, 74.5%). The aggregate HER2 positivity (score 3+) rate was 9.0%. The aggregate HER2 equivocal (score 2+) rate was 14.5%. Of 81 equivocal (score 2+) cases, 70 (86.4%) were nonamplified. CONCLUSIONS.­: The data from this study provide multi-institutional benchmark data to assist laboratories performing periodic comparisons as part of a quality management program. Overall expression rates were generally similar to those of other published reports, with the exception of the ER-negative and HER2-positive rates, both of which were somewhat lower.

Delta-6-desaturase activity and arachidonic acid synthesis are increased in human breast cancer tissue.

Omega-6 (n-6) arachidonic acid (AA) and its pro-inflammatory metabolites, including prostaglandin E2 (PGE(2)), are known to promote tumorigenesis. Delta-6 desaturase (D6D) is the rate-limiting enzyme for converting n-6 linoleic acid (LA) to AA. Our objective was to determine if AA synthesis, specifically D6D activity, and PGE(2) levels are increased in cancerous breast tissue, and whether these variables differ between estrogen receptor positive (ER+) and negative (ER-) breast cancers. Gas chromatography was performed on surgical breast tissue samples collected from 69 women with breast cancer. Fifty-four had ER+ breast cancer, and 15 had ER- breast cancer. Liquid chromatography-mass spectrometry was used to determine PGE(2) levels. Lipid analysis revealed higher levels of LA metabolites (C18:3 n-6, C20:3 n-6, and AA) in cancerous tissue than in adjacent noncancerous tissue (P < 0.01). The ratio of LA metabolites to LA, a measure of D6D activity, was increased in cancerous tissue, suggesting greater conversion of LA to AA (P < 0.001), and was higher in ER- than in ER+ patients, indicating genotype-related trends. Similarly, PGE(2) levels were increased in cancerous tissue, particularly in ER- patients. The results showed that the endogenous AA synthetic pathway, D6D activity, and PGE(2) levels are increased in breast tumors, particularly those of the ER- genotype. These findings suggest that the AA synthetic pathway and the D6D enzyme in particular may be involved in the pathogenesis of breast cancer. The development of drugs and nutritional interventions to alter this pathway may provide new strategies for breast cancer prevention and treatment.

The role of chemoprevention in modifying the risk of breast cancer in women with atypical breast lesions.

Women with atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), and severe ADH are at increased risk of breast cancer, but a systematic quantification of this risk and the efficacy of chemoprevention in the clinical setting is still lacking. The objective of this study is to evaluate a woman's risk of breast cancer based on atypia type and to determine the effect of chemoprevention in decreasing this risk. Review of 76,333 breast pathology reports from three institutions within Partners Healthcare System, Boston, from 1987 to 2010 using natural language processing was carried out. This approach identified 2,938 women diagnosed with atypical breast lesions. The main outcome of this study is breast cancer occurrence. Of the 2,938 patients with atypical breast lesions, 1,658 were documented to have received no chemoprevention, and 184/1,658 (11.1 %) developed breast cancer at a mean follow-up of 68 months. Estimated 10-year cancer risks were 17.3 % with ADH, 20.7 % with ALH, 23.7 % with LCIS, and 26.0 % with severe ADH. In a subset of patients treated from 1999 on (the chemoprevention era), those who received no chemoprevention had an estimated 10-year breast cancer risk of 21.3 %, whereas those treated with chemoprevention had a 10-year risk of 7.5 % (p < 0.001). Chemoprevention use significantly reduced breast cancer risk for all atypia types (p < 0.05). The risk of breast cancer with atypical breast lesions is substantial. Physicians should counsel patients with ADH, ALH, LCIS, and severe ADH about the benefit of chemoprevention in decreasing their breast cancer risk.

Laboratory Staff Turnover: A College of American Pathologists Q-Probes Study of 23 Clinical Laboratories.

CONTEXT.­: Knowledge of laboratory staff turnover rates are important to laboratory medical directors and hospital administrators who are responsible for ensuring adequate staffing of their clinical laboratories. The current turnover rates for laboratory employees are unknown. OBJECTIVE.­: To determine the 3-year average employee turnover rates for clinical laboratory staff and to survey the types of institutional human resource practices that may be associated with lower turnover rates. DESIGN.­: We collected data from participating laboratories spanning a 3-year period of 2015-2017, which included the number of full-time equivalent (FTE) staff members that their laboratories employed in several personnel and departmental categories, and the number of laboratory staff FTEs who vacated each of those categories that institutions intended to refill. We calculated the 3-year average turnover rates for all laboratory employees, for several personnel categories, and for major laboratory departmental categories, and assessed the potential associations between 3-year average all laboratory staff turnover rates with institutional human resource practices. RESULTS.­: A total of 23 (20 US and 3 international) participating institutions were included in the analysis. Among the 21 participants providing adequate turnover data, the median of the 3-year average turnover rate for all laboratory staff was 16.2%. Among personnel categories, ancillary staff had the lowest median (11.1% among 21 institutions) and phlebotomist staff had the highest median (24.9% among 20 institutions) of the 3-year average turnover rates. Among laboratory departments, microbiology had the lowest median (7.8% among 18 institutions) and anatomic pathology had the highest median (14.3% among 14 institutions) of the 3-year average turnover rates. Laboratories that developed and communicated clear career paths to their employees and that funded external laboratory continuing education activities had significantly lower 3-year average turnover rates than laboratories that did not implement these strategies. CONCLUSIONS.­: Laboratory staff turnover rates among institutions varied widely. Two human resource practices were associated with lower laboratory staff turnover rates.

Breast Specimen Processing and Reporting With an Emphasis on Margin Evaluation: A College of American Pathologists Survey of 866 Laboratories.

CONTEXT: - The College of American Pathologists (CAP) developed protocols for reporting pathologic characteristics of breast cancer specimens, including margin status. The Society of Surgical Oncology (SSO) and the American Society for Radiation Oncology (ASTRO) published treatment guidelines regarding margins in patients with invasive cancer; and SSO, ASTRO, and the American Society of Clinical Oncology (ASCO) recently published guidelines for patients with ductal carcinoma in situ. OBJECTIVE: - To assess current practices among pathologists with regard to the processing/reporting of breast specimens, assess compliance with CAP cancer protocols, and assess alignment with SSO/ASTRO and SSO/ASTRO/ASCO guidelines. DESIGN: - A survey concerning breast specimen processing/reporting was distributed to pathologists enrolled in the CAP Performance Improvement Program in Surgical Pathology. RESULTS: - Ninety-four percent (716 of 764 respondents) and 91% (699 of 769 respondents) define positive margins as "tumor on ink" for invasive cancer and ductal carcinoma in situ, respectively, in compliance with CAP cancer protocols and with SSO/ASTRO and SSO/ASTRO/ASCO guidelines. Of 791 respondents who provided details regarding methods for margin evaluation, 608 (77%) exclusively examine perpendicular margins, facilitating guideline compliance. However, 183 of 791 respondents (23%) examine en face margins in at least a subset of specimens, which may preclude guideline compliance in some cases. When separate cavity (shave) margins are examined, while 517 of 586 respondents (88%) ink these specimens, 69 of 586 (12%) do not, and this may also preclude guideline compliance in some cases. CONCLUSIONS: - A substantial proportion of survey participants report margin status for breast cancer specimens in a manner consistent with CAP cancer protocols, and in alignment with SSO/ASTRO and SSO/ASTRO/ASCO guidelines. However, there are opportunities for some laboratories to modify procedures in order to facilitate more complete adherence to guidelines.

Nipple-Invasive Primary Carcinomas: Clinical, Imaging, and Pathologic Features of Breast Carcinomas Originating in the Nipple.

Context Patients choosing to retain the nipple when undergoing therapeutic or prophylactic mastectomy are at risk for cancers arising at that site. Objective To identify cases of invasive carcinoma arising within the nipple and to investigate their clinical, imaging, biologic, and staging features. Design Carcinomas were identified by prospective review of surgical and consult cases at 4 hospitals. Results The 24 patients identified presented with symptoms related to the nipple. Mammography did not detect the cancer in most cases. Ten patients (42%) had skin changes from ductal carcinoma in situ involving nipple skin (Paget disease), with small foci of invasion into the dermis, and 6 of those 10 carcinomas (60%) stained positive for human epidermal growth factor receptor 2 (HER2). The remaining 14 patients (58%) presented with a nipple mass or with skin changes. These were larger invasive carcinomas of both ductal and lobular types. Only 2 of those 14 carcinomas (14%) were HER2+. Three of 15 patients (20%) undergoing lymph node biopsy had a single metastasis. No patients have had recurrent disease. Conclusions Rare, invasive, primary nipple carcinomas typically present as subtle nipple thickening or an exudative crust on the skin. Imaging studies are often nonrevealing. A variety of histologic and biologic types of carcinomas occur, similar to cancers arising deeper in the breast. Although the carcinomas invaded into the dermis, some with skin ulceration, the likelihood of lymph node metastasis was no higher than carcinomas of similar sizes. Patients who choose to preserve their nipple(s) should be aware of the possibility of breast cancer arising at that site and to bring any observed changes to the attention of their health care providers.

Quality Assurance in Breast Pathology: Lessons Learned From a Review of Amended Reports.

CONTEXT: -A review of amended pathology reports provides valuable information regarding defects in the surgical pathology process. OBJECTIVE: -To review amended breast pathology reports with emphasis placed on interpretative errors and their mechanisms of detection. DESIGN: -All amended pathology reports for breast surgical specimens for a 5-year period at a large academic medical center were retrospectively identified and classified based on an established taxonomy. RESULTS: -Of 12 228 breast pathology reports, 122 amended reports were identified. Most (88 cases; 72%) amendments were due to noninterpretative errors, including 58 report defects, 12 misidentifications, and 3 specimen defects. A few (34 cases; 27.9%) were classified as misinterpretations, including 14 major diagnostic changes (11.5% of all amendments). Among major changes, there were cases of missed microinvasion or small foci of invasion, missed micrometastasis, atypical ductal hyperplasia overcalled as ductal carcinoma in situ, ductal carcinoma in situ involving sclerosing adenosis mistaken for invasive carcinoma, lymphoma mistaken for invasive carcinoma, and amyloidosis misdiagnosed as fat necrosis. Nine major changes were detected at interpretation of receptor studies and were not associated with clinical consequences. Three cases were associated with clinical consequences, and of note, the same pathologist interpreted the corresponding receptor studies. CONCLUSIONS: -Review of amended reports was a useful method for identifying error frequencies, types, and methods of detection. Any time that a case is revisited for ancillary studies or other reasons, it is an opportunity for the surgical pathologist to reconsider one's own or another's diagnosis.

Professional Practice Evaluation for Pathologists: The Development, Life, and Death of the Evalumetrics Program.

CONTEXT: - In 2008, the Joint Commission (JC) implemented a standard mandating formal monitoring of physician professional performance as part of the process of granting and maintaining practice privileges. OBJECTIVE: - To create a pathology-specific management tool to aid pathologists in constructing a professional practice-monitoring program, thereby meeting the JC mandate. DESIGN: - A total of 105 College of American Pathologists (CAP)-defined metrics were created. Metrics were based on the job descriptions of pathologists' duties in the laboratory, and metric development was aided by experience from the Q-Probes and Q-Tracks programs. The program was offered in a Web-based format, allowing secure data entry, customization of metrics, and central data collection for future benchmarking. RESULTS: - The program was live for 3 years, with 347 pathologists subscribed from 61 practices (median, 4 per institution; range, 1-35). Subscribers used 93 of the CAP-defined metrics and created 109 custom metrics. The median number of CAP-defined metrics used per pathologist was 5 (range, 1-43), and the median custom-defined metrics per pathologist was 2 (range, 1-5). Most frequently, 1 to 3 metrics were monitored (42.7%), with 20% each following 4 to 6 metrics, 5 to 9 metrics, or greater than 10 metrics. Anatomic pathology metrics were used more commonly than clinical pathology metrics. Owing to low registration, the program was discontinued in 2016. CONCLUSIONS: - Through careful vetting of metrics it was possible to develop a pathologist-specific management tool to address the JC mandate. While this initial product failed, valuable metrics were developed and implementation knowledge was gained that may be used to address new regulatory requirements for emerging value-based payment systems.

Association of angiogenesis and disease outcome in node-positive breast cancer patients treated with adjuvant cyclophosphamide, doxorubicin, and fluorouracil: a Cancer and Leukemia Group B correlative science study from protocols 8541/8869.

PURPOSE: Increased microvessel density (MVD), a reflection of tumor angiogenesis, is associated with diminished relapse-free and overall survival (OS) in several subsets of breast cancer patients. However, the utility of this assay in node-positive patients treated with adjuvant cyclophosphamide, doxorubicin, and fluorouracil (CAF) has not been well studied. PATIENTS AND METHODS: Immunostaining for factor VIII-related antigen was performed on tissue sections from a subset of node-positive patients who received one of three dose/schedule regimens of CAF during participation in Cancer and Leukemia Group B protocol 8541. Sections from 577 cancers exhibited acceptable tumor and immunostaining quality and were included in the study. Each section was examined quantitatively for MVD as well as non-quantitatively by scoring the presence or absence of a prominent vascular pattern. RESULTS: MVD counts were not associated with relapse-free or OS in univariate analysis. The presence of a prominent plexiform vascular pattern was correlated with decreased OS (P =.0085) in univariate analysis, but this pattern was not an independent prognostic indicator of survival in multivariate analysis. No apparent clinically important interactions between measures of angiogenesis, other prognostic factors, administration of tamoxifen, and chemotherapy dose were observed. CONCLUSION: Assessment of angiogenesis does not provide useful information regarding prognosis in node-positive breast cancer patients treated with adjuvant CAF, nor do these measures predict which patients will benefit from dose intensification or addition of tamoxifen.