Pathologist's health-care value in the triage of Oncotype DX® testing: a value-based pathology study of tumour biology with outcomes.

AIMS: Pathologists provide expert tissue assessment of breast cancer, yet their value to guide the appropriate use of breast cancer gene expression profile tests (GEPT) is underutilised. The specific aims of this study are to report morpho-immunohistological characteristics of breast tumours with Oncotype DX® (ODx) recurrence scores (RS) of 10 or fewer (ultra-low risk) and 25 or fewer (low risk) in order to determine if pathologists can identify prospectively patient tumours that do not require ODx testing. METHODS AND RESULTS: Oncotype DX® cases with RS < 10 from 2005 to 2010 comprised 441 of 2594 (17%) of clinical cases; this cohort had 5 years' follow-up and was treated with endocrine therapy alone. Tumours were analysed for tumour type, Nottingham grade, mitosis score (MS) semi-quantitative (H-score) hormone receptor content and Magee equation 3. Knowledge derived from this data set was used to develop algorithms in order to identify prospectively tumours with RS of 10 or fewer or 25 or fewer. Thirty-four per cent of tumours were low-grade special types, while the remainder were enriched with high hormone receptor content with MS of 1. These algorithmic selection criteria identified correctly all patient cases below the chemotherapy cut-point, i.e. RS < 25, indicating that these oncotype test orders were an unnecessary cost. CONCLUSIONS: This unique study demonstrates that (i) pathologists add great value to triage breast cancer for GEPT; and (ii) can identify prospectively low-grade tumour biology with high sensitivity and high specificity for those cases which do not require chemotherapy (RS < 25) using MS and hormone receptor content.

Synchronous Bilateral Tubal Serous Carcinomas in a Patient With Exon 13 Duplication and Loss of Function of BRCA1.

We report the first case of distinct, synchronous serous carcinomas of the adnexa arising in a patient with a family history of breast and ovarian cancer and a germline loss of function mutation in BRCA1. Illustrating an exceedingly rare phenomenon of synchronous high-grade carcinomas with distinct histomorphologic, immunohistochemical and cytogenetic features, the case serves as a point of departure for the discussion of phenotypic patterns of carcinomas arising in BRCA1 mutation carriers. We also review patient management, including the importance of risk-reducing salpingo-oophorectomy in women with deleterious BRCA1 mutations, as well as the potential need for an intraoperative pathologic assessment to find occult, high-grade carcinomas in this setting.

NCI SEER-Linked Virtual Tissue Repository Pilot.

BACKGROUND: The Surveillance, Epidemiology, and End Results (SEER) Program with the National Cancer Institute tested whether population-based cancer registries can serve as honest brokers to acquire tissue and data in the SEER-Linked Virtual Tissue Repository (VTR) Pilot. METHODS: We collected formalin-fixed, paraffin-embedded tissue and clinical data from patients with pancreatic ductal adenocarcinoma (PDAC) and breast cancer (BC) for two studies comparing cancer cases with highly unusual survival (≥5 years for PDAC and ≤30 months for BC) to pair-matched controls with usual survival (≤2 years for PDAC and ≥5 years for BC). Success was defined as the ability for registries to acquire tissue and data on cancer cases with highly unusual outcomes. RESULTS: Of 98 PDAC and 103 BC matched cases eligible for tissue collection, sources of attrition for tissue collection were tissue being unavailable, control paired with failed case, second control that was not requested, tumor necrosis ≥20%, and low tumor cellularity. In total, tissue meeting the study criteria was obtained for 70 (71%) PDAC and 74 (72%) BC matched cases. For patients with tissue received, clinical data completeness ranged from 59% for CA-19-9 after treatment to >95% for margin status, whether radiation therapy and chemotherapy were administered, and comorbidities. CONCLUSIONS: The VTR Pilot demonstrated the feasibility of using SEER cancer registries as honest brokers to provide tissue and clinical data for secondary use in research. Studies using this program should oversample by 45% to 50% to obtain sufficient sample size and targeted population representation and involve subspecialty matter expert pathologists for tissue selection.

Male Breast Cancer.

Objectives: A clinicopathologic study with an emphasis on tumor immunohistochemical profile is presented. Methods: Sixty-one cases of male invasive breast cancers were studied. Median age of the cohort was 65 years. Results: Ninety-seven percent were estrogen receptor positive+ and 10% human epidermal growth factor receptor 2 positive. The individual diagnostic marker positivity was 98% for GATA-binding protein 3, 95% for androgen receptor, 90% for progesterone receptor, 88% for deleted in pancreatic cancer 4, 75% for gross cystic disease fluid protein 15, 72% for cytokeratin 7, 55% for mammaglobin, and 15% for vimentin and Wilms tumor protein 1. Caudal type homeobox 2 protein, cytokeratin 20, Napsin A, paired box gene 8, prostate-specific antigen, thyroid transcription factor 1, and uroplakin II were negative in all cases. Survival analyses showed tumor stage, receptor status, and Nottingham prognostic index to be prognostic. The overall survival was 70%, but the breast cancer­specific survival was 92% (mean follow-up, 59 months); 33% developed second malignancy. The immunohistochemistry profile was similar to female breast cancers. Conclusions: The second malignancies in this cohort affected overall survival and suggest the possibility of other germline mutations in addition to BRCA2 in male patients with breast cancer.

The Value of Papanicolaou Tests in the Diagnosis of Endometrial Carcinoma: A Large Study Cohort From an Academic Medical Center.

OBJECTIVES: To determine on a large scale whether routine cervical Papanicolaou (Pap) tests play a role in endometrial carcinoma diagnosis. METHODS: A retrospective search of an academic women's hospital pathology archive for cases of surgically resected endometrial carcinoma with Pap smears within 36 months before the histologic diagnosis was performed. Demographic features, Pap test results, and tumor features were recorded. RESULTS: We identified 554 (30.5%) of 1,817 cases of endometrial carcinoma with documented Pap test results within 36 months before histologic diagnosis. Among these 554 patients, 405 (73.0%) had Pap test results within 5 months before histologic diagnosis. In total, 154 (38%) cases demonstrated abnormal glandular cells, and 25 (6.2%) had only benign endometrial cells in women 40 years or older. The presence of glandular abnormality on the Pap test is significantly correlated with tumor size, tumor type, depth of invasion, presence of cervical involvement, and presence of lymphovascular invasion (P < .05). The rate of detecting abnormal glandular cells was higher in cases with a high International Federation of Gynecology and Obstetrics (FIGO) stage than in cases with a low FIGO stage (47.5% vs 35.5%; P < .05). CONCLUSIONS: The Pap test may play a role in the detection of endometrial carcinoma, especially for those with cervical involvement, lymphovascular invasion, and/or advanced stage.