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A real-time trial of a cancer blood test Cancers diagnosed early are often more responsive to treatment. Blood tests that detect molecular markers of cancer have successfully identified individuals already known to have the disease. Lennon et al. conducted an exploratory study that more closely reflects the way in which such blood tests would be used in the future. They evaluated the feasibility and safety of incorporating a multicancer blood test into the routine clinical care of 10,000 women with no history of cancer. Over a 12-month period, the blood test detected 26 cancers of different types. A combination of the blood test and positron emission tomography–computed tomography (PET-CT) imaging led to surgical removal of nine of these cancers. Use of the blood test did not result in a large number of futile follow-up procedures. Science , this issue p. eabb9601

Purpose The clinical utility of screening unselected individuals for pathogenic BRCA1/2 variants has not been established. Data on cancer risk management behaviors and diagnoses of BRCA1/2-associated cancers can help inform assessments of clinical utility. Methods Whole-exome sequences of participants in the MyCode Community Health Initiative were reviewed for pathogenic/likely pathogenic BRCA1/2 variants. Clinically confirmed variants were disclosed to patient–participants and their clinicians. We queried patient–participants’ electronic health records for BRCA1/2-associated cancer diagnoses and risk management that occurred within 12 months after results disclosure, and calculated the percentage of patient–participants of eligible age who had begun risk management. Results Thirty-seven MyCode patient–participants were unaware of their pathogenic/likely pathogenic BRCA1/2 variant, had not had a BRCA1/2-associated cancer, and had 12 months of follow-up. Of the 33 who were of an age to begin BRCA1/2-associated risk management, 26 (79%) had performed at least one such procedure. Three were diagnosed with an early-stage, BRCA1/2-associated cancer—including a stage 1C fallopian tube cancer—via these procedures. Conclusion Screening for pathogenic BRCA1/2 variants among unselected individuals can lead to occult cancer detection shortly after disclosure. Comprehensive outcomes data generated within our learning healthcare system will aid in determining whether population-wide BRCA1/2 genomic screening programs offer clinical utility.

1563 Background: Blood-based tests may enable minimally invasive detection of multiple cancer types. One such test, CancerSEEK, employs ctDNA and protein biomarkers for this purpose. Test performance has been evaluated in women without a history of cancer in an ongoing prospective study called DETECT-A. The introduction of such blood tests holds promise, and their future utility lies in augmenting, not displacing, standard-of-care (SOC) cancer screening. One important safety concern is that a negative test result could provide false reassurance that discourages adherence to SOC cancer screening. To investigate this possibility, we studied delivery of mammography to DETECT-A participants before and after receipt of a negative CancerSEEK result. Methods: DETECT-A screened 10,000 women aged 65-75 using CancerSEEK. Participants completed a survey about cancer screening at enrollment and at one-year post-enrollment. We analyzed only those participants who had received a negative CancerSEEK result, were insured by Geisinger Health Plan (GHP), and had completed both surveys. GHP claims data were used to identify mammograms performed within one year prior-to and post-enrollment. Overall utilization was determined by combining claims and survey data at enrollment and one-year post-enrollment. In addition to comparing SOC screening rates pre- versus post-testing, we evaluated the impact of primary care physician (PCP) type (Geisinger versus any other institution), as screening reminder mechanisms differ between institutions. Results: Of the 2,241 participants who met analysis criteria, 73.6% (n = 1,650) had a mammogram in the year before enrollment while a significantly great number (79.3%, n = 1,777) did so during the one-year follow-up (χ2(1) = 59.05, p < 0.001). At enrollment, there were 591 participants who had not had a mammogram completed in the previous year, but 404 (68.4%) of them did have a mammogram during the one-year follow-up. The rate of change in mammography utilization did not differ between those who had a Geisinger versus a non-Geisinger PCP (χ2(2) = 1.83, p = 0.40). Conclusions: Participants in a study using a novel blood test for earlier cancer detection had a significantly higher rate of annual mammography after study enrollment and testing. These results indicate that introduction of a minimally invasive ctDNA and protein biomarker-based cancer screening test may engender greater, not lesser, utilization of SOC cancer screening. Further study is required to understand the root causes of increased utilization in this context.

Key Points Question Can population-level genomic screening identify those at risk for disease? Findings In this cross-sectional study of an unselected population cohort of 50 726 adults who underwent exome sequencing, pathogenic and likely pathogenic BRCA1 and BRCA2 variants were found in a higher proportion of patients than was previously reported. Meaning Current methods to identify BRCA1/2 variant carriers may not be sufficient as a screening tool; population genomic screening for hereditary breast and ovarian cancer may better identify patients at high risk and provide an intervention opportunity to reduce mortality and morbidity., Importance Detection of disease-associated variants in the BRCA1 and BRCA2 (BRCA1/2) genes allows for cancer prevention and early diagnosis in high-risk individuals. Objectives To identify pathogenic and likely pathogenic (P/LP) BRCA1/2 variants in an unselected research cohort, and to characterize the features associated with P/LP variants. Design, Setting, and Participants This is a cross-sectional study of adult volunteers (n = 50 726) who underwent exome sequencing at a single health care system (Geisinger Health System, Danville, Pennsylvania) from January 1, 2014, to March 1, 2016. Participants are part of the DiscovEHR cohort and were identified through the Geisinger MyCode Community Health Initiative. They consented to a research protocol that included sequencing and return of actionable test results. Clinical data from electronic health records and clinical visits were correlated with variants. Comparisons were made between those with (cases) and those without (controls) P/LP variants in BRCA1/2. Main Outcomes Prevalence of P/LP BRCA1/2 variants in cohort, proportion of variant carriers not previously ascertained through clinical testing, and personal and family history of relevant cancers among BRCA1/2 variant carriers and noncarriers. Results Of the 50 726 health system patients who underwent exome sequencing, 50 459 (99.5%) had no expected pathogenic BRCA1/2 variants and 267 (0.5%) were BRCA1/2 carriers. Of the 267 cases (148 [55.4%] were women and 119 [44.6%] were men with a mean [range] age of 58.9 [23-90] years), 183 (68.5%) received clinically confirmed results in their electronic health record. Among the 267 participants with P/LP BRCA1/2 variants, 219 (82.0%) had no prior clinical testing, 95 (35.6%) had BRCA1 variants, and 172 (64.4%) had BRCA2 variants. Syndromic cancer diagnoses were present in 11 (47.8%) of the 23 deceased BRCA1/2 carriers and in 56 (20.9%) of all 267 BRCA1/2 carriers. Among women, 31 (20.9%) of 148 variant carriers had a personal history of breast cancer, compared with 1554 (5.2%) of 29 880 noncarriers (odds ratio [OR], 5.95; 95% CI, 3.88-9.13; P, This cross-sectional study investigates the ascertainment of pathogenic and likely pathogenic BRCA1/2 variants among US adults enrolled in the MyCode Community Health Initiative.

Seventy-six patients with intraductal carcinoma (DCIS) of the breast have been observed for 83 months (range 50-141) following treatment by lumpectomy (L) only (21), L and breast irradiation (XRT) (27), or mastectomy (28). All represented examples of DCIS retrieved after pathologic examination of a much larger cohort of patients with stage I and II invasive breast cancer enrolled in NSABP protocol 6. Local breast recurrences were similar for women with DCIS and those from this cohort at a similar period of follow-up with invasive cancer treated by L only (43% vs. 39%) and L + XRT (7% vs. 10%). The presence of moderate/marked comedonecrosis was suggestively related to local breast recurrence (P = .07). This latter was significantly reduced for patients receiving post L XRT (P = .01). All local breast recurrences in this study and 29 of 31 recorded by others occurred at or close to the site of extirpation of the index cancer minimizing multicentricity as a contraindication for the conservative surgical treatment of DCIS. Survival rates which were similar for patients with DCIS regardless of form of local treatment were better than that observed for negative node patients with invasive cancer enrolled in protocol 6. Thus, DCIS is a less, not more, ominous disease than invasive cancer. This and other features of its natural history indicate that it would be a contradiction to treat invasive cancer but not DCIS conservatively.

METHODS: This was a retrospective study of 294,765 female breast cancer patients from the National Cancer Database from 2010 to 2012 with known hormone (HR) and HER2 receptor status. Patients were divided into two groups based on receptor status: 1) Aggressive: HR+, HER2+; HR-, HER2+; or HR-, HER2(Triple Negative) and 2) Less aggressive: HR+, HER2-. The primary outcome was extent of local therapy: mastectomy or BCT. Propensity score matching was performed.

That sweat gland type tumors occur occasionally in the breast is not surprising, as the breast and cutaneous sweat glands are embryologically related. Cylindromas present most commonly as solitary and sporadic dermal nodules on the face and scalp. Cases of multiple cylindromas are dominantly inherited, and the neoplasms are referred to as "turban tumors" when multiple lesions cover the scalp. Primary cylindroma of the breast has been reported once in the past. To the best of our knowledge, the fine needle aspiration cytology of primary breast cylindroma and its occurrence in the setting of familial cylindromatosis have not previously been reported.A 59-year-old woman presented with an ill-defined left breast mass. She had a personal and family history of dermal cylindromas on the head and face. Fine needle aspiration cytology demonstrated small, uniform cells with oval nuclei and finely granular cytoplasm, with some cells arranged around conspicuous cylinders of dense, acellular material. Excisional biopsy was recommended to exclude adenoid cystic carcinoma. Tissue biopsy revealed a benign cylindroma arising in breast parenchyma.Fine needle aspiration cytology of cylindroma very closely mimics that of adenoid cystic carcinoma. Although extremely rare, primary breast cylindroma is another entity to be included in the cytologic differential diagnosis of bland, basaloid cells associated with globular, extracellular material, a finding most commonly associated with adenoid cystic carcinoma.

Pancreaticoduodenectomy with revascularization of the hepatic artery and portal vein was performed on a 17-year-old girl with giant nonfunctioning islet cell tumor of the pancreas. She had a remote history of neonatal hypoglycemia leading to mental retardation and a right Wilms' tumor resected at 8 months. Serum pancreatic polypeptide levels were elevated. Her postoperative course was complicated by an ischemic perforation of the colon, which did not infect her prosthetic vascular grafts. The relationship between her neonatal hypoglycemia, Wilms' tumor, and subsequent islet cell neoplasm is unclear. © 1993 Wiley-Liss, Inc.

A case of an inguinal dermoid cyst presenting as an incarcerated inguinal hernia in a 18-year-old boy is reported. A differential diagnosis of masses in the inguinal region is discussed and includes not only hernias but also gynecologic and vascular lesions. Dermoid cysts must be included in the differential diagnosis. Histologically, these cysts are characterized by an external lining composed of squamous epithelium with an underlying fibroconnective tissue containing hair follicles, sebaceous, eccrine, and apocrine glands. The presence of all the skin appendages in these cysts distinguishes them from epidermoid and sebaceous cysts. The lack of structures foreign to skin differentiates them from dermoids (benign cystic teratomas) in the ovarian, testicular, retroperitoneal, and sacrococcygeal region.

• Adenoid cystic carcinoma of the breast is a rare neoplasm, with only 140 cases having been reported to date. Data on 123 of these cases are reviewed herein and another case is presented in detail. Several features distinguish this type of breast cancer from more typical histologic types and suggest that it may have a unique tumor behavior. The prognosis appears to be favorable and the incidence of axillary lymph node involvement is lower. Distant metastases are uncommon, but they tend to occur without prior lymph node involvement. This lack of prognostic significance for negative axillary lymph nodes underscores the need for other prognostic markers in this disease and suggests that axillary dissection can be eliminated in most cases. Similarities to typical breast cancer include the incidence of local recurrence and the lack of effect of surgical treatment on distant metastases and overall survival. These data suggest that breast-conserving treatment may be applicable to adenoid cystic carcinoma. ( Arch Surg . 1992;127:233-235)