Trajectory of Subsequent Breast Cancer Diagnoses in a Diverse Patient Cohort with Breast Atypia.

BACKGROUND: Proliferative breast atypical lesions, including atypical ductal hyperplasia (ADH) and lobular intraepithelial neoplasms (LIN), represent benign entities that confer an elevated risk of ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC). However, the timing of disease progression is variable and risk factors associated with the trajectory of disease are unknown. METHODS: Patients diagnosed with ADH or LIN from 1992 to 2017 at an academic center were identified. Early progression was defined as DCIS or IBC diagnosed within 5 years following the initial atypia diagnosis. Unadjusted cancer-free survival was estimated using the Kaplan-Meier method. Demographics, clinicopathologic features, and use of chemoprevention were compared between the early and late development groups. RESULTS: Overall, 418 patients were included-73.7% with ADH and 26.3% with LIN. Over a median follow up of 92.1 months, 71/418 (17.0%) patients developed IBC (57.7%) or DCIS (42.3%). Almost half (47.9%, 34/71) were diagnosed within 5 years of their initial atypia diagnosis, and 52.1% (37/71) were diagnosed after 5 years. Patient and atypia characteristics were not associated with rate of events or time to events. There was a trend of early events being more often ipsilateral (76.5% early vs. 54.1% late; p = 0.13) versus contralateral. CONCLUSIONS: In a large cohort of patients with breast atypia and long-term follow up, 17% experienced subsequent breast events, with approximately half of the events occurring within the first 5 years following the initial atypia diagnosis. Clinical features were not associated with the trajectory to subsequent events, supporting that atypia signals both local and overall malignancy risk.

Accuracy of the Breast Cancer Surveillance Consortium Model Among Women with LCIS.

PURPOSE: The Breast Cancer Surveillance Consortium (BCSC) model predicts risk of invasive breast cancer risk based on age, race, family history, breast density, and history of benign breast disease, including lobular carcinoma in situ (LCIS). However, validation studies for this model included few women with LCIS. We sought to evaluate the accuracy of the BCSC model among this cohort. METHODS: Women with LCIS diagnosed between 1983 and 2017 were identified from a prospectively maintained database. The BCSC score was calculated; those with prior breast cancer, unknown breast density, age < 35 years or > 74 years, or with history of chemoprevention use were excluded. The Kaplan-Meier method was used to estimate incidence rates. Time-dependent receiver operating characteristic (ROC) analysis was used to analyze the discriminative capacity of the model. RESULTS: 1302 women with LCIS were included. At a median follow-up of 7 years, 152 women (12%) developed invasive cancer (6 with bilateral disease). Cumulative incidences of invasive breast cancer were 7.1% (95% CI 5.6-8.7) and 13.3% (95% CI 10.9-15.6), respectively, and the median BCSC risk scores were 4.9 and 10.4, respectively, at 5 and 10 years. The median 10-year BCSC score was significantly lower than the 10-year Tyrer-Cuzick score (10.4 vs 20.8, p < 0.001). The ROC curve scores (AUC) for BCSC at 5 and 10 years were 0.59 (95% CI 0.52-0.66) and 0.58 (95% CI 0.52-0.64), respectively. CONCLUSION: The BCSC model has moderate accuracy in predicting invasive breast cancer risk among women with LCIS with fair discrimination for risk prediction between individuals.

Lobular carcinoma in situ: diagnostic criteria and molecular correlates.

Lobular neoplasia (LN) is an atypical proliferation of small, dyscohesive epithelial cells within the terminal duct lobular unit (TDLU), with or without pagetoid extension and encompasses both lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH). LN is a non-obligate precursor of invasive breast carcinoma and the diagnosis of LN confers an increased risk of invasive carcinoma development, compared to the general population. Diagnostic challenges arise in the accurate classification of LCIS into classic, pleomorphic and florid subtypes, in distinguishing between LCIS and ductal carcinoma in situ (DCIS) and in the appropriate use and interpretation of E-cadherin immunohistochemistry. Due to the paucity of robust data on the natural history of LCIS, and hence its clinical significance, the management is often pragmatic rather than entirely evidence-based and requires a multidisciplinary approach. In this review, we discuss the clinicopathologic and molecular features of LCIS and address the key challenges that arise in the diagnosis and management of LCIS.

The Tyrer-Cuzick Model Inaccurately Predicts Invasive Breast Cancer Risk in Women With LCIS.

BACKGROUND: The Tyrer-Cuzick model has been shown to overestimate risk in women with atypical hyperplasia, although its accuracy among women with lobular carcinoma in situ (LCIS) is unknown. We evaluated the accuracy of the Tyrer-Cuzick model for predicting invasive breast cancer (IBC) development among women with LCIS. METHODS: Women with LCIS participating in surveillance from 1987 to 2017 were identified from a prospectively maintained database. Tyrer-Cuzick score (version 7) was calculated near the time of LCIS diagnosis. Patients with prior or concurrent breast cancer, a BRCA mutation, receiving chemoprevention, or with pleomorphic LCIS were excluded. Invasive cancer-free probability was estimated using the Kaplan-Meier method. RESULTS: A total of 1192 women with a median follow-up of 6 years (interquartile range [IQR] 2.5-9.9) were included. Median age at LCIS diagnosis was 49 years (IQR 45-55), 88% were white; 37% were postmenopausal, 28% had ≥ 1 first-degree family member with breast cancer, and 13% had ≥ 2 second-degree family members with breast cancer. In total, 128 patients developed an IBC; median age at diagnosis was 54 years (IQR 49-61). Five- and 10-year cumulative incidences of invasive cancer were 8% (95% confidence interval [CI] 6-9%) and 14% (95% CI 12-17%), respectively. The median Tyrer-Cuzick 10-year risk score was 20.1 (IQR 17.4-24.3). Discrimination measured by the C-index was 0.493, confirming that the Tyrer-Cuzick model is not well calibrated in this patient population. CONCLUSIONS: The Tyrer-Cuzick model is not accurate and may overpredict IBC risk for women with LCIS, and therefore should not be used for breast cancer risk assessment in this high-risk population.

Membranous overexpression of S100A10 is associated with a high-grade cellular status of breast carcinoma.

S100A10 promotes tumor invasion in various cancers. Although genetic studies on S100A10 in breast carcinoma (BC) have been used for molecular biological classification, immunohistochemical studies are lacking. We aimed to identify the correlation between S100A10 expression in BC and various pathological parameters, including morphological features to determine histological grade (HG). Immunostained serial paraffin-embedded tissue sections from 176 cases of resected BC or normal mammary ducts (controls) were assessed for the membrane expression of S100A10. Of the 176 cases, 125 conventional infiltrating ductal carcinomas were chosen, comprising 67 (53.6%) S100A10-positive tumors, whereas normal mammary ducts were S100A10-negative. S100A10 immunoreactivity in ductal carcinoma in situ (n = 51) was similar to that of invasive carcinoma. The distinct membrane-immunopositivity was correlated with high HG, severe nuclear pleomorphism, frequent mitotic counts, high Ki-67 labeling index, HER2/neu overexpression, and low estrogen receptor status (P < 0.05), but not with tubular formation, pT categories, node metastasis, vessel permeation, and pStage. Membrane overexpression of S100A10 in BC correlates with the high-grade morphological and molecular status of the carcinoma cell rather than stromal invasion and architectural deviation. Evidence points to the use of S100A10 as a biomarker representing a high-grade cellular status of BC.

Case report of polymyalgia rheumatica in a male patient with three different neoplasms treated with pembrolizumab.

In this manuscript we aim to describe a particular case of a 63 years-old man who developed three different malignancies (one was a rare case of breast cancer) among nearly five years. In particular, for the diagnosis of melanoma, he was treated with pembrolizumab, a PD-1 inhibitor. After few months of treatment with pembrolizumab, the patient reported the onset of musculoskeletal symptoms such as inflammatory pain at the shoulders and morning stiffness, with raised CRP and ESR and imaging evidence of bursitis and tenosynovitis. A polymyalgia-like syndrome was diagnosed. Understanding if these manifestations are linked to the use of pembrolizumab or to a paraneoplastic syndrome, and how to manage the patient, was the real challenge.

Change in health-related quality of life in older women after diagnosis of a small breast cancer.

BACKGROUND: Screening mammography reduces breast cancer mortality at the cost of frequent false-positive results that lead to unnecessary medical procedures, and the treatment of indolent breast cancers that would never threaten life or health. Earlier diagnosis generally permits less disruptive treatment, but it is possible that even the diagnosis of a very small breast cancer could significantly adversely impact health-related quality of life (HRQOL) in older women. METHODS: The authors compared changes in HRQOL measured by either the Medical Outcomes Study 36-Item Short Form (SF-36) or the Veterans Rand 12-item Health Survey (VR-12) between 198 women diagnosed with in situ or invasive breast cancer measuring ≤1 cm and 36,814 matched controls using the National Cancer Institute's Surveillance, Epidemiology, and End Results cancer registry linked with the Medicare Health Outcomes Survey. RESULTS: The mean age of the cases and controls was 75 years. The SF-36/VR-12 physical component score 12 was found to decrease by 1.6 points between the baseline and follow-up surveys for the controls compared with 3.2 points for women diagnosed with small breast cancers (P = .016). A 2-point decline is recognized as the minimally significant difference for this measure. On multivariable analysis, diagnosis of a small breast cancer was found to be one of the strongest predictors of a significant decrease in both the physical and mental domains of HRQOL (P = .012 and P = .023, respectively). CONCLUSIONS: Receiving the diagnosis of even a very small breast cancer significantly impacts the physical and mental domains of HRQOL in older women. This finding can inform discussions regarding the relative benefits and costs of screening mammography in older women.

Evaluating the Rate of Upgrade to Invasive Breast Cancer and/or Ductal Carcinoma In Situ Following a Core Biopsy Diagnosis of Non-classic Lobular Carcinoma In Situ.

BACKGROUND: A diagnosis of non-classic lobular carcinoma in situ (NC-LCIS) encompasses a variety of lesions with poorly characterized natural history. We evaluated upgrade rates and factors associated with upgrade to malignancy following a core biopsy diagnosis of NC-LCIS, and its natural history. METHODS: Upon Institutional Review Board approval, pathology databases were searched for NC-LCIS core biopsy diagnoses (carcinoma in situ [CIS], CIS with ductal and lobular features [CIS/DLF], pleomorphic LCIS [P-LCIS], variant LCIS [V-LCIS], LCIS with necrosis). Cases with available core and excision pathology were included, while cases with concurrent ipsilateral invasive carcinoma (IC), ductal carcinoma in situ (DCIS), and/or atypical ductal hyperplasia were excluded. RESULTS: Overall, 121 NC-LCIS cases were identified from 1998 to 2017. We excluded 46 cases with concurrent cancer; 75 patients with 76 NC-LCIS core biopsy diagnoses followed by excision formed our study cohort. Median age was 56 years (range 41-83), and all imaging findings were classified as Breast Imaging Reporting and Data System 4; calcifications were the most common biopsy indication (80%). Excision yielded malignancy in 27 (36%) patients (IC 17, 63%; DCIS alone 10, 37%). We were unable to identify radiologic or pathologic features predictive of upgrade. Of 49 pure NC-LCIS cases, 15 (31%) had mastectomy, 9 (18%) had excision and radiation, and 25 (51%) had excision alone. At a median follow-up of 58 months (range 1-224), 1/25 (4%) patients with excision alone developed ipsilateral DCIS 14 months later. CONCLUSIONS: In this series of NC-LCIS, 36% of cases were upgraded, supporting routine excision. We were unable to identify predictors of upgrade. Among 25 patients with pure NC-LCIS, only one patient developed a future ipsilateral cancer. Further study of the natural history of NC-LCIS is warranted.

The Influence of Age on the Histopathology and Prognosis of Atypical Breast Lesions.

BACKGROUND: Although several prognostic variables and risk factors for breast cancer are age-related, the association between age and risk of cancer with breast atypia is controversial. This study aimed to compare the type of breast atypia and risk of underlying or subsequent breast cancer by age. METHODS: Adult women with breast atypia (atypical ductal hyperplasia, atypical lobular hyperplasia, and lobular carcinoma in situ) at a single institution from 2008 to 2017 were stratified by age at initial diagnosis: <50 y, 50-70 y, and >70 y. Regression modeling was used to estimate the association of age with risk of underlying carcinoma or subsequent cancer diagnosis. RESULTS: A total of 530 patients with atypia were identified: 31.1% < 50 y (n = 165), 58.1% 50-70 y (n = 308), and 10.8% > 70 y (n = 57). The proportion of women with atypical ductal hyperplasia steadily increased with age, compared with atypical lobular proliferations (P = 0.04). Of those with atypia on needle biopsy, the overall rate of underlying carcinoma was 17.5%. After adjustment, older age was associated with a greater risk of underlying carcinoma (odds ratio: 1.028, 95% confidence interval: 1.003-1.053; P = 0.03). Of those confirmed to have atypia on surgical excision, the overall rate of a subsequent cancer diagnosis was 15.7%. Age was not associated with a long-term risk for breast cancer (P = 0.48) or the time to a subsequent diagnosis of carcinoma (log-rank P = 0.41). CONCLUSIONS: Although atypia diagnosed on needle biopsy may be sufficient to warrant surgical excision, older women may be at a greater risk for an underlying carcinoma, albeit the long-term risk for malignancy associated with atypia does not appear to be affected by age.

Breaking bad news of a breast cancer diagnosis over the telephone: an emerging trend.

PURPOSE: This study evaluated how breast cancer diagnoses were shared with patients. METHODS: Current members of the Dr. Susan Love Research Foundation's Army of Women cohort were sent one email with a link to a survey assessing how their breast cancer diagnosis was communicated, a description of their support system during treatment, basic demographic information, and breast cancer diagnosis details. RESULTS: Participants (n = 2896) were more likely to be given their diagnosis over the telephone in more recent years (OR 1.07, 95% CI 1.06-1.08). Up until about 10 years ago (1967-2006), breast cancer diagnoses were communicated in person more often than by telephone. Since 2006, more than half of participants learned about their diagnosis over the telephone. From 2015 to 2017, almost 60% of participants learned about their diagnosis over the telephone. Among those who heard the news in person, a steady 40% were alone. Characteristics of those who received the news over the telephone included having identified support members, heterosexual identity, and a diagnosis of in situ breast cancer. CONCLUSIONS: Receiving a telephone call about breast cancer diagnosis may be the norm rather than the exception in health care today. Trends in practice, as well as current best practices based primarily on expert opinion, may not provide optimal care for women diagnosed with breast cancer. Patient outcome research to guide future practice, such as the impact of modes of delivery of bad news, is urgently needed to determine appropriate patient-centered approaches for notification of breast cancer diagnoses.

Overview of breast cancer.

Each year, more than 250,000 women in the United States are diagnosed with invasive breast cancer. Although overall mortality for breast cancer patients has declined, it is still the second most common cause of cancer death in women. This article provides an overview of nonmetastatic breast cancer in women, including general features, diagnostic considerations, and treatments for the most common breast cancer subtypes.

Rapid virtual hematoxylin and eosin histology of breast tissue specimens using a compact fluorescence nonlinear microscope.

Up to 40% of patients undergoing breast conserving surgery for breast cancer require repeat surgeries due to close to or positive margins. The lengthy processing required for evaluating surgical margins by standard paraffin-embedded histology precludes its use during surgery and therefore, technologies for rapid evaluation of surgical pathology could improve the treatment of breast cancer by reducing the number of surgeries required. We demonstrate real-time histological evaluation of breast cancer surgical specimens by staining specimens with acridine orange (AO) and sulforhodamine 101 (SR101) analogously to hematoxylin and eosin (H&E) and then imaging the specimens with fluorescence nonlinear microscopy (NLM) using a compact femtosecond fiber laser. A video-rate computational light absorption model was used to produce realistic virtual H&E images of tissue in real time and in three dimensions. NLM imaging could be performed to depths of 100 µm below the tissue surface, which is important since many surgical specimens require subsurface evaluation due to contamination artifacts on the tissue surface from electrocautery, surgical ink, or debris from specimen handling. We validate this method by expert review of NLM images compared to formalin-fixed, paraffin-embedded (FFPE) H&E histology. Diagnostically important features such as normal terminal ductal lobular units, fibrous and adipose stromal parenchyma, inflammation, invasive carcinoma, and in situ lobular and ductal carcinoma were present in NLM images associated with pathologies identified on standard FFPE H&E histology. We demonstrate that AO and SR101 were extracted to undetectable levels after FFPE processing and fluorescence in situ hybridization (FISH) HER2 amplification status was unaffected by the NLM imaging protocol. This method potentially enables cost-effective, real-time histological guidance of surgical resections.

Observation versus excision of lobular neoplasia on core needle biopsy of the breast.

PURPOSE: Controversy surrounds management of lobular neoplasia (LN), [atypical lobular hyperplasia (ALH) or lobular carcinoma in situ (LCIS)], diagnosed on core needle biopsy (CNB). Retrospective series of pure ALH and LCIS reported "upgrade" rate to DCIS or invasive cancer in 0-40%. Few reports document radiologic/pathologic correlation to exclude cases of discordance that are the likely source of most upgrades, and there is minimal data on outcomes with follow-up imaging and clinical surveillance. METHODS: Cases of LN alone on CNB (2001-2014) were reviewed. CNB yielding LN with other pathologic findings for which surgery was indicated were excluded. All patients had either surgical excision or clinical follow-up with breast imaging. All cases included were subject to radiologic-pathologic correlation after biopsy. RESULTS: 178 cases were identified out of 62213 (0.3%). 115 (65%) patients underwent surgery, and 54 (30%) patients had surveillance for > 12 months (mean = 55 months). Of the patients who underwent surgical excision, 13/115 (11%) were malignant. Eight of these 13 found malignancy at excision when CNB results were considered discordant (5 DCIS, and 3 invasive lobular carcinoma), with the remainder, 5/115 (4%), having a true pathologic upgrade: 3 DCIS, and 2 microinvasive lobular carcinoma. Among 54 patients not having excision, 12/54 (22%) underwent subsequent CNB with only 1 carcinoma found at the initial biopsy site. CONCLUSIONS: Surgical excision of LN yields a low upgrade rate when careful consideration is given to radiologic/pathologic correlation to exclude cases of discordance. Observation with interval breast imaging is a reasonable alternative for most cases.

Diagnosis and Management of High-Risk Breast Lesions.

Atypical hyperplasia (AH) and lobular carcinoma in situ (LCIS) are nonmalignant breast lesions that confer a 4- to 10-fold increased risk for breast cancer in women. Often, AH and LCIS are diagnosed through breast biopsy due to a mammographic or palpable finding. Although AH and LCIS are benign breast disease, further management is necessary due to their high-risk nature and premalignant potential. Over the decades, management of AH and LCIS has changed as more is learned about these disease processes. This review explores the studies evaluating the risk for breast cancer in women with AH or LCIS and the clinical management of these lesions, which can include a combination of surgical excision, surveillance, and risk-reduction therapy.

Initiation of and adherence to tamoxifen and aromatase inhibitor therapy among elderly women with ductal carcinoma in situ.

BACKGROUND: The National Surgical Adjuvant Breast and Bowel Project B35 and International Breast Cancer Intervention Studies II Ductal Carcinoma In Situ trials showed similar treatment effects of anastrozole and tamoxifen in reducing cancer recurrence risk among ductal carcinoma in situ (DCIS) patients. Studies have shown low levels of hormone therapy drug initiation for DCIS patients, but the current body of literature lacks information on the 5-year adherence rates for these drugs from population-based studies. METHODS: This study evaluated the initiation and 5-year adherence levels for women aged 66 to 85 years who had been diagnosed with estrogen receptor (ER)-positive DCIS between 2007 and 2011 according to the Surveillance, Epidemiology, and End Results and Texas Cancer Registry databases linked to Medicare claims. Chi-square tests, trend tests, and logistic regression were used to identify factors associated with treatment initiation. RESULTS: There were 2871 women with ER-positive DCIS, and approximately 45% began treatment with tamoxifen or aromatase inhibitors (AIs) within 1 year of their DCIS diagnosis. The median age was 73 years for the users and 75 years for the nonusers. Women aged 66 to 70 years who underwent lumpectomy and radiation therapy were significantly more likely to initiate hormone therapy. The initiation of therapy was also significantly associated with patients' geographic location, education, marital status, diagnosis year, and race/ethnicity. Among users, adherence decreased from 67% in the first year to 30% in the fifth year. CONCLUSIONS: Initiation and adherence levels for tamoxifen or AIs among older women with ER-positive DCIS are low. Future studies should develop methods to ensure that informed discussions take place between health care providers and patients regarding hormonal therapy for cancer prevention. Cancer 2017;123:940-47. © 2016 American Cancer Society.

Pleomorphic lobular carcinoma in situ of the breast: a single institution experience with clinical follow-up and centralized pathology review.

PURPOSE: The natural history of pleomorphic lobular carcinoma in situ (PLCIS) remains largely unknown. METHODS: A pathology database search (1995-2012) was performed to identify patients diagnosed with an LCIS variant. Patients with synchronous breast cancer and/or no evidence of pleomorphism were excluded. Original slides were re-evaluated by three pathologists to identify a consensus cohort of PLCIS. Borderline lesions with focal atypia were classified as LCIS with pleomorphic features (LCIS-PF). Clinical data were obtained from medical records. RESULTS: From 233 patients, we identified 32 with an LCIS variant diagnosis and no concurrent breast cancer. Following review, 16 cases were excluded due to lack of pleomorphism. The remaining 16 were classified as PLCIS (n = 11) and LCIS-PF (n = 5). 12/16 patients were treated with surgical excision ± chemoprevention. Patients with a prior breast cancer history and those having mastectomy were excluded from outcome analysis. Among the remaining 7 patients with PLCIS/LCIS-PF, 4/7 (57%) developed ipsilateral breast cancer at a median follow-up of 67 months. Median age at the time of breast cancer diagnosis was 56 years old and median time from PLCIS/LCIS-PF to cancer diagnosis was 59 months (range 45-66 months). The four cancers included 1 invasive lobular carcinoma (ILC), 1 microinvasive ILC, 1 invasive ductal carcinoma, and 1 ductal carcinoma in situ. CONCLUSIONS: We confirm that PLCIS in isolation is indeed a rare entity, further contributing to the difficulty in determining the actual risk conferred by this lesion. Long-term follow-up data on larger cohorts are needed to define standardized management and outcomes for patients with PLCIS.

GT198 Expression Defines Mutant Tumor Stroma in Human Breast Cancer.

Human breast cancer precursor cells remain to be elucidated. Using breast cancer gene product GT198 (PSMC3IP; alias TBPIP or Hop2) as a unique marker, we revealed the cellular identities of GT198 mutant cells in human breast tumor stroma. GT198 is a steroid hormone receptor coactivator and a crucial factor in DNA repair. Germline mutations in GT198 are present in breast and ovarian cancer families. Somatic mutations in GT198 are present in ovarian tumor stromal cells. Herein, we show that human breast tumor stromal cells carry GT198 somatic mutations and express cytoplasmic GT198 protein. GT198(+) stromal cells share vascular smooth muscle cell origin, including myoepithelial cells, adipocytes, capillary pericytes, and stromal fibroblasts. Frequent GT198 mutations are associated with GT198(+) tumor stroma but not with GT198(-) tumor cells. GT198(+) progenitor cells are mostly capillary pericytes. When tested in cultured cells, mutant GT198 induces vascular endothelial growth factor promoter, and potentially promotes angiogenesis and adipogenesis. Our results suggest that multiple lineages of breast tumor stromal cells are mutated in GT198. These findings imply the presence of mutant progenitors, whereas their descendants, carrying the same GT198 mutations, are collectively responsible for forming breast tumor microenvironment. GT198 expression is, therefore, a specific marker of mutant breast tumor stroma and has the potential to facilitate diagnosis and targeted treatment of human breast cancer.

The superparamagnetic iron oxide tracer: a valid alternative in sentinel node biopsy for breast cancer treatment.

The European Union has determined that from 2016 breast cancer patients should be treated in Specialist Breast Units that achieve the minimum standards for the mandatory quality indicators as defined by Eusoma. The existing standard for axillary lymph node staging in breast cancer is sentinel node biopsy (SNB), performed using Technetium-sulphur colloid (99m Tc) alone or with blue dye. The major limits of radioisotope consist in the problems linked to radioactivity, in the shortage of tracer and nuclear medicine units. Among existing alternative tracers, SentiMag® , which uses superparamagnetic iron oxide particles, can represent a valid option for SNB. We conducted a paired, prospective, multicentre study to evaluate the non-inferiority of SentiMag® vs. 99m Tc. The primary end point was the detection rate (DR) per patient. The study sample consists of 193 women affected by breast carcinoma with negative axillary assessment. The concordance rate per patients between 99m Tc and SentiMag® was 97.9%. The DR per patient was 99.0% for 99m Tc and 97.9% for SentiMag® . SentiMag® appears to be non-inferior to the radiotracer and safe. While 99m Tc remains the standard, SentiMag® DR appears adequate after a minimum learning curve. In health care settings where nuclear medicine units are not available, SentiMag/Sienna+® allows effective treatment of breast cancer patients.

Variability in Pathologists' Interpretations of Individual Breast Biopsy Slides: A Population Perspective.

BACKGROUND: The effect of physician diagnostic variability on accuracy at a population level depends on the prevalence of diagnoses. OBJECTIVE: To estimate how diagnostic variability affects accuracy from the perspective of a U.S. woman aged 50 to 59 years having a breast biopsy. DESIGN: Applied probability using Bayes' theorem. SETTING: B-Path (Breast Pathology) Study comparing pathologists' interpretations of a single biopsy slide versus a reference consensus interpretation from 3 experts. PARTICIPANTS: 115 practicing pathologists (6900 total interpretations from 240 distinct cases). MEASUREMENTS: A single representative slide from each of the 240 cases was used to estimate the proportion of biopsies with a diagnosis that would be verified if the same slide were interpreted by a reference group of 3 expert pathologists. Probabilities of confirmation (predictive values) were estimated using B-Path Study results and prevalence of biopsy diagnoses for women aged 50 to 59 years in the Breast Cancer Surveillance Consortium. RESULTS: Overall, if 1 representative slide were used per case, 92.3% (95% CI, 91.4% to 93.1%) of breast biopsy diagnoses would be verified by reference consensus diagnoses, with 4.6% (CI, 3.9% to 5.3%) overinterpreted and 3.2% (CI, 2.7% to 3.6%) underinterpreted. Verification of invasive breast cancer and benign without atypia diagnoses is highly probable; estimated predictive values were 97.7% (CI, 96.5% to 98.7%) and 97.1% (CI, 96.7% to 97.4%), respectively. Verification is less probable for atypia (53.6% overinterpreted and 8.6% underinterpreted) and ductal carcinoma in situ (DCIS) (18.5% overinterpreted and 11.8% underinterpreted). LIMITATIONS: Estimates are based on a testing situation with 1 slide used per case and without access to second opinions. Population-adjusted estimates may differ for women from other age groups, unscreened women, or women in different practice settings. CONCLUSION: This analysis, based on interpretation of a single breast biopsy slide per case, predicts a low likelihood that a diagnosis of atypia or DCIS would be verified by a reference consensus diagnosis. This diagnostic grey zone should be considered in clinical management decisions in patients with these diagnoses. PRIMARY FUNDING SOURCE: National Cancer Institute.