Discordance of Oncotype DX scores in synchronous bilateral and unilateral multifocal breast cancers.

PURPOSE: Oncotype DX, a 21-gene expression profiling test, has become standard of care in the management of estrogen receptor (ER)-positive breast cancer. In multifocal tumors, it is unclear whether testing of the different foci is necessary. We evaluated the concordance of Oncotype DX recurrence scores (RS) between 2 tumor foci in synchronous bilateral or unilateral multifocal tumors and characterized pathological predictors of discordance. METHODS: We reviewed 713 ER+, HER2- primary invasive breast cancer patients with Oncotype RS and identified 17 bilateral synchronous patients (34 tumors) and 13 unilateral multifocal patients (26 tumors) with available Oncotype RS on all foci. Discordance in Oncotype RS between synchronous tumors was recorded and associations with clinicopathologic features including tumor size, histology, Nottingham histologic grade, progesterone receptor staining, and Ki67 index were analyzed. RESULTS: Bilateral synchronous tumors were present in older patients (median age 59 years) and had larger tumor (median size 17 mm) and more discordant histology (10/17, 59%) as compared to unilateral multifocal tumors (median age 49 years, p < 0.01; median tumor size 12 mm, p = 0.01; discordant histology 2/13, 15%, p = 0.03). Oncotype RS were discordant in 47% (8/17) of bilateral and 54% (7/13) of unilateral multifocal tumors. Concordant Oncotype RS was associated with similar histologic grade and Ki67 index in 78% (7/9) of bilateral and 100% (6/6) of multifocal tumors. In contrast, only 25% (2/8) of bilateral (p = 0.06) and 14% (1/7) of unilateral multifocal (p < 0.01) cases with discordant Oncotype RS had concordant histology grades and Ki67 levels. In synchronous tumors with discordant Oncotype RS and Ki67 index, all (4/4) foci with higher RS had higher Ki67 index. CONCLUSION: Discordance of Oncotype RS is common in both bilateral and unilateral multifocal breast cancer and is likely associated with discordant histologic grade or Ki67.

The Milan System for Reporting Salivary Gland Cytopathology: the experience of a tertiary cancer center with emphasis on non-mucinous cysts and improving diagnostic results.

INTRODUCTION: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was introduced in 2018 to standardize cytology reporting and guide patient treatment. We aimed to evaluate the utility of this system applied to patients at our cancer center. MATERIALS AND METHODS: We retrospectively reviewed cases of salivary gland fine-needle aspirations (FNAs) performed in our institution (2019-2022). All were performed by radiologists and immediately assessed for specimen adequacy. The cytologic findings were classified into the MSRSGC except for non-mucinous cystic contents (NMCC) where the lesion was radiologically consistent with a cyst and totally collapsed after FNA. Such lesions were categorized as non-neoplastic (NN) instead of non-diagnostic (ND). The cytologic findings were compared to corresponding histologic findings (212 available cases), and the risk of malignancy was calculated. RESULTS: Five hundred five FNAs were categorized as: 25 (4.95%) ND; 86 (17.03%) NN, of which 39 were NMCC; 9 (1.78%) atypia of undetermined significance; 138 (27.33%) benign neoplasms; 57 (11.29%) salivary gland neoplasm of undetermined malignant potential; 16 (3.17%) suspicious for malignancy; and 174 (34.46%) malignant. The risk of malignancy rates for the following categories were: ND, 40%; NN, 25%; atypia of undetermined significance, 0%; benign neoplasms, 1%; salivary gland neoplasm of undetermined malignant potential, 54.54%; suspicious for malignancy, 90.9%; and malignant, 100%. Thirty-one NMCC with available follow-up resolved/remained stable. CONCLUSIONS: Our results validate the reproducibility of the MSRSGC applied in our cancer center. Based on the benign course of cysts with NMCC, we propose that such cases be categorized as NN, provided the cyst is totally resolved after FNA.

Short-Term Biomarker Modulation Study of Dasatinib for Estrogen Receptor-Negative Breast Cancer Chemoprevention.

Objective: Risk-reducing therapy with selective estrogen receptor (ER) modulators and aromatase inhibitors reduce breast cancer risk. However, the effects are limited to ER-positive breast cancer. Therefore, new agents with improved toxicity profiles that reduce the risk in ER-negative breast cancers are urgently needed. The aim of this prospective, short-term, prevention study was to evaluate the effect of dasatinib, an inhibitor of the tyrosine kinase Src, on biomarkers in normal (but increased risk) breast tissue and serum of women at high risk for a second, contralateral primary breast cancer. Materials and Methods: Women with a history of unilateral stage I, II, or III ER-negative breast cancer, having no active disease, and who completed all adjuvant therapies were eligible. Patients underwent baseline fine-needle aspiration (FNA) of the contralateral breast and serum collection for biomarker analysis and were randomized to receive either no treatment (control) or dasatinib at 40 or 80 mg/day for three months. After three months, serum collection and breast FNA were repeated. Planned biomarker analysis consisted of changes in cytology and Ki-67 on breast FNA, and changes in serum levels of insulin-like growth factor 1 (IGF-1), IGF-binding protein 1, and IGF-binding protein 3. The primary objective was to evaluate changes in Ki-67 and secondary objective included changes in cytology in breast tissue and IGF-related serum biomarkers. Toxicity was also evaluated. Results: Twenty-three patients started their assigned treatments. Compliance during the study was high, with 86.9% (20/23) of patients completing their assigned doses. Dasatinib was well tolerated and no drug-related grade 3 and 4 adverse events were observed. Since only one patient met the adequacy criteria for the paired FNA sample, we could not evaluate Ki-67 level or cytological changes. No significant change in serum biomarkers was observed among the three groups. Conclusion: Dasatinib was well tolerated but did not induce any significant changes in serum biomarkers. The study could not fulfill its primary objective due to an inadequate number of paired FNA samples. Further, larger studies are needed to evaluate the effectiveness of Src inhibitors in breast cancer prevention.

The Utility of Fine Needle Aspiration (FNA) Biopsy in the Diagnosis of Mediastinal Lesions.

Fine needle aspiration is a minimally invasive, low-morbidity, and cost-efficient technique for the sampling of mediastinal lesions. Additionally, ancillary testing on FNA samples can be used for the refinement of diagnoses and for treatment-related purposes (flow cytometry, cytogenetics, immunohistochemistry, and molecular diagnostics). Mediastinal lesions, however, can show a variety of lineages and morphologic features, giving rise to diagnostic dilemmas. As a result, the differential diagnosis can vary widely and becomes especially challenging due to the smaller sample size on FNA and the variability in component sampling. For appropriate patient management and to determine the correct treatment strategies, accurate pathologic diagnoses are paramount. In this review, we present the cytomorphologic features together with the immunophenotypic findings of mediastinal lesions, with emphasis on the diagnostic challenges and pitfalls in FNA cytology samples, including smears and cell block sections.

The utility of claudin-4 versus MOC-31 and Ber-EP4 in the diagnosis of metastatic carcinoma in cytology specimens.

BACKGROUND: Claudin-4 is a sensitive and specific marker for carcinoma in effusion cytology. The authors examined the diagnostic use of claudin-4 versus MOC-31 and Ber-EP4 by comparing their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in differentiating carcinoma from mesothelioma and benign/mesothelial hyperplasia in effusion specimens. METHODS: This retrospective study comprised a cohort of 229 cytology specimens, including 211 effusion fluid and 18 fine-needle aspiration specimens. Cytologic categories included 134 carcinoma, 28 mesothelioma, 46 indefinite (suspicious and atypical), and 21 benign. Cell block sections were stained for claudin-4 and compared with those previously stained for MOC-31 and Ber-EP4. Indefinite cases were further reclassified based on clinical and pathologic findings into benign (26 cases), mesothelioma (11 cases), and carcinoma (nine cases). RESULTS: None of the mesotheliomas (0/39) or benign effusions (0/47) were positive for claudin-4, whereas 134 of the 143 carcinoma specimens were positive. Compared to MOC-31 and Ber-EP4, claudin-4 had the highest specificity and PPV (100% for each), followed by Ber-EP4. Claudin-4 showed high sensitivity (93.7%), albeit lower than MOC-31. MOC-31 had the lowest specificity and PPV but the highest sensitivity and NPV. Ber-EP4 had the lowest sensitivity (91.6%). CONCLUSIONS: Claudin-4 can be used as a single marker for carcinoma with high sensitivity and superior specificity compared with MOC-31 and Ber-EP4. Mesothelial lineage can be ruled out when claudin-4 is positive. In equivocal cytology samples with few scattered cells of interest, a panel of claudin-4 and Ber-EP4 results in the highest combined sensitivity and specificity.

Randomized Phase III Trial Evaluating Radiation Following Surgical Excision for Good-Risk Ductal Carcinoma In Situ: Long-Term Report From NRG Oncology/RTOG 9804.

PURPOSE: To our knowledge, NRG/RTOG 9804 is the only randomized trial to assess the impact of whole breast irradiation (radiation therapy [RT]) versus observation (OBS) in women with good-risk ductal carcinoma in situ (DCIS), following lumpectomy. Long-term results focusing on ipsilateral breast recurrence (IBR), the primary outcome, are presented here. PATIENTS AND METHODS: Eligible patients underwent lumpectomy for DCIS that was mammogram detected, size ≤ 2.5 cm, final margins ≥ 3 mm, and low or intermediate nuclear grade. Consented patients were randomly assigned to RT or OBS. Tamoxifen use was optional. Cumulative incidence was used to estimate IBR, log-rank test and Gray's test to compare treatments, and Fine-Gray regression for hazard ratios (HRs). RESULTS: A total of six hundred thirty-six women were randomly assigned from 1999 to 2006. Median age was 58 years and mean pathologic DCIS size was 0.60 cm. Intention to use tamoxifen was balanced between arms (69%); however, actual receipt of tamoxifen varied, 58% RT versus 66% OBS (P = .05). At 13.9 years' median follow-up, the 15-year cumulative incidence of IBR was 7.1% (95% CI, 4.0 to 11.5) with RT versus 15.1% (95% CI, 10.8 to 20.2) OBS (P = .0007; HR = 0.36; 95% CI, 0.20 to 0.66); and for invasive LR was 5.4% (95% CI, 2.7 to 9.5) RT versus 9.5% (95% CI, 6.0 to 13.9) OBS (P = .027; HR = 0.44; 95% CI, 0.21 to 0.91). On multivariable analysis, only RT (HR = 0.34; 95% CI, 0.19 to 0.64; P = .0007) and tamoxifen use (HR = 0.45; 95% CI, 0.25 to 0.78; P = .0047) were associated with reduced IBR. CONCLUSION: RT significantly reduced all and invasive IBR for good-risk DCIS with durable results at 15 years. These results are not an absolute indication for RT but rather should inform shared patient-physician treatment decisions about ipsilateral breast risk reduction in the long term following lumpectomy.

HER2 testing in breast cancers: comparison of assays and interpretation using ASCO/CAP 2013 and 2018 guidelines.

PURPOSE: HER2 overexpression and gene amplification are routinely tested by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), respectively. In addition, HER2 mRNA expression is also tested by the Oncotype DX assay. Discordance between laboratories among the different assays remains a problem. To improve the routine HER2 reporting, the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) updated their guidelines in 2018. Our study will compare concordance of HER2 status by IHC and FISH using ASCO/CAP 2013 and 2018 guidelines with Oncotype DX. METHODS: We retrospectively reviewed 657 estrogen receptor positive primary breast cancer cases with available Oncotype DX tests between 2011 and 2018. Medical records were reviewed for HER2 results by IHC, FISH, and Oncotype DX. The HER2 results by different assays and between 2013 and 2018 guidelines were compared. RESULTS: Of the 657 cases, 280 were tested by IHC, FISH, and Oncotype DX. HER2-equivocal cases by IHC 2013 guidelines were all negative (67/67, 100%) by FISH 2018 guidelines and by Oncotype DX. HER2-equivocal cases by FISH 2013 guidelines were all negative (16/16, 100%) by FISH 2018 guidelines, while 15/16 (93.8%) negative and 1/16 (6.2%) equivocal by Oncotype DX. The HER2-equivocal and HER2-negative groups were similar in age, gender, histology, grade, and Ki67 score. CONCLUSIONS: HER2 concordance was highest between Oncotype DX (99.6%) and FISH per 2018 guidelines. This suggests that the ASCO/CAP 2018 guidelines improved the accurate stratification of HER2-equivocal cases.

Biomarker Modulation Study of Celecoxib for Chemoprevention in Women at Increased Risk for Breast Cancer: A Phase II Pilot Study.

In preclinical studies, celecoxib has been associated with reduced risk of breast cancer. In this study, the aim was to assess the biomodulatory effect of celecoxib on blood and benign breast tissue biomarkers in women at increased risk for breast cancer. Women at increased risk for breast cancer [5-year Gail risk score of >1.67%, history of atypical hyperplasia, lobular carcinoma in situ, or previous estrogen receptor (ER)-negative breast cancer] were treated with celecoxib at 400 mg orally twice daily for 6 months. Participants underwent random periareolar fine needle aspiration and blood draw at baseline and at 6 months for analysis of biomarkers: serum levels of insulin-like growth factor 1 (IGF-1), IGF-binding protein 1 (IGFBP-1), and IGFBP-3; tissue expression of Ki-67 and ER; as well as cytology. Forty-nine patients were eligible for analysis. Median IGFBP-1 levels increased significantly from 6.05 ng/mL at baseline to 6.93 ng/mL at 6 months (P = 0.04), and median IGFBP-3 levels decreased significantly from 3,593 ng/mL to 3,420 ng/mL (P = 0.01). We also detected favorable changes in cytology of 52% of tested sites after 6 months of celecoxib therapy. No changes in tissue Ki-67 and ER expression levels were observed. No grade 3 or 4 toxicity was recorded. Celecoxib was well tolerated and induced favorable changes in serum biomarkers as well as cytology in this pilot phase II trial. A phase IIb placebo-controlled study with celecoxib could be considered for women at increased risk for breast cancer.

Mammary mesenchymal and fibroepithelial lesions: An illustrated cytomorphologic update with differential diagnoses.

The Uniform Approach to Breast Fine Needle Aspiration Biopsy was put forward by a learned group of breast physicians in 1997. This landmark manuscript focused predominantly on diagnosis and reporting of mammary epithelial lesions. Today, most American practitioners turn initially to core biopsy rather than aspiration biopsy for the first line diagnosis of solid breast lesions; however, recent efforts from the International Academy of Cytology have produced a system called the Standardized Reporting of Breast Fine Needle Aspiration Biopsy Cytology (colloquially labeled in 2017 as the "Yokohama System"), suggesting a new interest in breast fine needle aspiration (FNA), especially in resource limited settings or clinical practice settings with experienced breast cytopathologists. Fibroepithelial lesions of the breast comprise a heterogeneous group of biphasic tumors with epithelial and stromal elements. Mesenchymal lesions of the breast include a variety of neoplasms of fibroblastic, myofibroblastic, endothelial, neural, adipocytic, muscular, and osteo-cartilaginous derivations. The cytology of mesenchymal breast lesions is infrequently described in the literature and is mainly limited to case reports and small series. This illustrated review highlights the cytologic features of fibroepithelial and mesenchymal mammary proliferations and discusses differential diagnoses and histomorphologic correlates.

Clinical Management of Mucocele-Like Lesions of the Breast with Limited or no Epithelial Atypia on Core Biopsy: Experience from Two Institutions.

PURPOSE: Mucocele-like lesions of the breast identified on core biopsy are rare high-risk lesions associated with variable upgrade rates to carcinoma on excision. We aimed to identify the clinicoradiopathological features that can help optimize management of this lesion. METHODS: We evaluated 50 mucocele-like lesions identified on core biopsies from two institutions, including 36 with no atypia and 14 with limited atypia. Outcome data from excision or clinicoradiological follow-up were reviewed with core biopsy results. RESULTS: Radiological targets were calcifications in 74% of cases, calcifications with associated mass or density in 16%, and mass in 10%. One of the 16 excised lesions without atypia on core biopsy, which was a mass lesion, was upgraded to mucinous carcinoma on excision. Of the 12 excised lesions with limited atypia, none were upgraded on excision. Among the lesions not excised, 20 without atypia had a median follow-up of 61 months, and 2 with limited atypia had follow-up of 97 and 109 months. None of these 22 patients had new development of their lesions on follow-up. The upgrade rate was 2% in our entire cohort, 3% for lesions without atypia, and 0% for lesions with limited atypia. CONCLUSIONS: Clinicoradiological surveillance can be appropriate when a mucocele-like lesion without atypia is identified on core biopsy for a non-mass lesion with pathological-radiological concordance. For mucocele-like lesions with limited atypia, a nonsurgical approach could be considered if the atypia by itself does not warrant excision. The latter recommendation requires careful clinicopathological correlation and support from additional studies.

Clinical presentation of ductal carcinoma in situ of breast with intraluminal crystalloids: Radiologic-histologic correlation.

Intraluminal crystalloids have rarely been described in the breast, particularly in cases with ductal carcinoma in situ (DCIS). We recently encountered a case of DCIS of the breast associated with numerous intraluminal crystalloids. The patient presented with a mass in the right breast, and microcalcifications were detected on screening and diagnostic mammograms; the patient underwent needle biopsies, lumpectomy, and skin-sparing mastectomy. Invasive ductal carcinoma associated with extensive DCIS was diagnosed. Multiple refractile, eosinophilic crystalloids, with variable morphologies including rectangular, triangular and needle-like with sharp borders, were observed within the lumina of DCIS, besides calcium phosphate microcalcifications. We report this case together with a literature review on crystalloid-containing lesions in breast and non-breast tissues. We also studied radiologic findings of these crystalloids using a specimen radiograph.

Flat epithelial atypia in directional vacuum-assisted biopsy of breast microcalcifications: surgical excision may not be necessary.

The aim of this study was to analyze the clinicopathological features of patients with flat epithelial atypia, diagnosed in directional vacuum-assisted biopsy targeting microcalcifications, to identify upgrade rate to in situ ductal or invasive breast carcinoma, and determine factors predicting carcinoma in the subsequent excision. We retrospectively evaluated the histological, clinical, and mammographic features of 69 cases from 65 women, with directional vacuum-assisted biopsy-diagnosed flat epithelial atypia with or without atypical ductal hyperplasia or atypical lobular hyperplasia, which underwent subsequent surgical excision. The extent and percentage of microcalcifications sampled by directional vacuum-assisted biopsy were evaluated by mammography. All biopsy and surgical excision slides were reviewed. The age of the women ranged from 40 to 85 years (mean 57 years). All patients presented with mammographically detected microcalcifications only, except in one case that had associated architectural distortion. Extent of calcifications ranged from <1 cm (n = 47), 1-3 cm (n = 15) to > 3 cm (n = 6), and no measurement (n = 1). A mean of 11 cores (range 6-25) was obtained from each lesion. Post-biopsy mammogram revealed >90% removal of calcifications in 81% of cases. Pure flat epithelial atypia represented nearly two-thirds of directional vacuum-assisted biopsy specimens (n = 43, 62%), while flat epithelial atypia coexisted with atypical ductal hyperplasia (18 cases, 26%), or atypical lobular hyperplasia (8 cases, 12%). Upon excision, none of the cases were upgraded to in situ ductal or invasive breast cancer. In one case, however, an incidental, tubular carcinoma (4 mm) was found away from biopsy site. Excluding this case, the upgrade rate was 0%. Our study adds to the growing evidence that diagnosis of flat epithelial atypia on directional vacuum-assisted biopsy for microcalcifications as the only imaging finding is not associated with a significant upgrade to carcinoma on excision, and therefore, excision may not be necessary. Additionally, excision may not be necessary for flat epithelial atypia with atypical ductal hyperplasia limited to ≤2 terminal duct-lobular units, if at least 90% of calcifications have been removed on biopsy.

Utility of endoscopic ultrasound-guided fine-needle aspiration of regional lymph nodes that are proximal to and far from the primary distal esophageal carcinoma.

Implications of assessing the proximal and far para-tracheal or sub-carinal nodes (para-tracheal [PTN] or sub-carinal [SCN]) associated with lower primary esophageal carcinomas (ECs) are unclear. To evaluate the value of endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) for PTN and SCN, we analyzed results by positron emission tomography (PET) avidity, 4 EUS node malignancy features, and EUS-FNA results in all patients with Siewert's I or II EC. Of 133 patients (PTN, n=102; SCN, n=31) with EUS-FNA, 47 (35%) patients had malignant node, leading to treatment modifications. EUS-FNA diagnosed significantly more patients with malignant nodes (p=0.02) even when PET and EUS features were combined. Among 94 PET-negative and EUS-negative patients, 9 (10%) had malignant EUS-FNA. At a minimum follow-up of 1 year, only 3 (5%) of 62 patients with benign EUS-FNA had evidence of malignancy in the nodal area of prior EUS-FNA. Patients with malignant EUS-FNA independently had a much shorter overall survival (OS) than those with benign EUS-FNA (p<0.001). Our data suggest that a benign EUS-FNA is highly accurate and need not be pursued further. However, malignant EUS-FNA of PTN/SCN was independently prognostic, conferred a shorter OS, and altered the management of 35% of patients.

Three-year risk of high-grade CIN for women aged 30 years or older who undergo baseline Pap cytology and HPV co-screening.

BACKGROUND: Papanicolaou (Pap) cytology and high-risk human papillomavirus (HPV) DNA cotesting for women aged ≥30 years are recommended for the prevention of cervical cancer. The objective of the current study was to evaluate the efficacy of this cotesting for predicting the risk of high-grade cervical intraepithelial neoplasia 3 (CIN3) during a 3-year follow-up period. METHODS: A retrospective database search identified women aged ≥30 years who had baseline HPV and Pap cytology cotesting results in 2007 or 2008 and for whom 3-year follow-up results were available. The cumulative 3-year risks of developing CIN-3 were calculated. RESULTS: The 3-year follow-up data after baseline Pap/HPV cotesting were available for 1986 women (mean age, 53 years). Of the 1668 women who had a baseline Pap-negative (Pap-)/HPV- cotesting result, 1561 (93.6%) had a follow-up Pap cytology result that was negative for intraepithelial lesions or malignancy. Of the 1530 women who had follow-up Pap/HPV cotesting, 1504 (98.3%) had a Pap-/HPV- result. The 3-year cumulative risk of developing CIN-3 was found to be highest for women with a baseline Pap-positive (Pap+)/HPV+ cotesting result (12.5%); the risk of CIN-3 was lower in those with a Pap-/HPV+ result (1.5%; P = .0032) or a Pap-/HPV- result (0.06%; P<.0001). The 3-year cumulative risk of CIN-3 was found to be significantly greater for women with an HPV+ result (4.8%) compared with those with an HPV- result (0.06%; P<.0001). CONCLUSIONS: Pap cytology and HPV cotesting are valuable for stratifying CIN-3 risk. Pap cytology and HPV co-screening at a 3-year screening interval appears to carry a low risk of CIN-3 for women who have a baseline Pap-/HPV- cotesting result. Cancer Cytopathol 2017;125:644-51. © 2017 American Cancer Society.

Prognostic significance of equivocal human epidermal growth factor receptor 2 results and clinical utility of alternative chromosome 17 genes in patients with invasive breast cancer: A cohort study.

BACKGROUND: The 2013 testing guidelines for determining the human epidermal growth factor receptor 2 (HER2) status include new cutoff points for the HER2/chromosome enumeration probe 17 (CEP17) ratio and the average HER2 copy number per cell, and they recommend using a reflex test with alternative chromosome 17 probes (Ch17Ps) to resolve equivocal HER2 results. This study sought to determine the clinical utility of alternative Ch17Ps in equivocal cases and the effects of equivocal results and/or a change in the HER2 status on patients' outcomes. METHODS: The University of Texas MD Anderson Cancer Center database of HER2 dual-probe fluorescence in situ hybridization results from 2000 to 2010 was searched for cases of invasive breast cancer with HER2/CEP17 ratios < 2 and average HER2 copy numbers < 6 per cell. Cases with HER2 copy numbers of 4 to < 6 (the definition of equivocal HER2 results) were analyzed with alternative Ch17Ps for Smith-Magenis syndrome and retinoic acid receptor α genes. Disease-free survival (DFS) and overall survival (OS) were evaluated with respect to the HER2 copy number with multivariate Cox proportional hazards regression. RESULTS: Among the 3630 patients meeting the inclusion criteria, 137 (4%) had equivocal HER2 results. With alternative Ch17Ps, 35 of 57 equivocal HER2 cases (61%) were upgraded to a positive HER2 status, and 22 cases (39%) remained unchanged. The 5-year DFS and OS adjusted hazard ratios (HRs) for copy numbers of 4 to < 6 versus < 4 were 0.6 (95% confidence interval [CI], 0.3-1.2) and 0.5 (95% CI, 0.2-1.0) with P values of .16 and .66, respectively. In comparison with HER2-negative cases, these CIs indicated that equivocal HER2 results were associated with either a protective effect (HR, < 0.5) or no effect (HR, 1.0). CONCLUSIONS: These findings rule out a significant deleterious effect of equivocal HER2 results. Alternative Ch17Ps may erroneously upgrade the HER2 status; therefore, they cannot be considered reliable in clinical practice. Cancer 2017;123:1115-1123. © 2016 American Cancer Society.

Comparison of the accuracy of US-guided biopsy of breast masses performed with 14-gauge, 16-gauge and 18-gauge automated cutting needle biopsy devices, and review of the literature.

OBJECTIVE: To compare the diagnostic accuracy of ultrasound (US)-guided core needle biopsy (CNB) of breast masses performed with 14-gauge, 16-gauge and 18-gauge needles. METHODS: We retrospectively reviewed the charts of 1,112 patients who underwent US-guided breast CNB with 14-gauge, 16-gauge and 18-gauge needles. Cases with surgical excision or a minimum of 2 years of imaging follow-up were included. Rates of sample inadequacy, discordance with surgical or imaging findings and upgrade of DCIS to invasive cancer or high-risk lesion to in situ or invasive cancer were computed for each needle size. RESULTS: The study included 703 CNBs: 203 performed with 14-gauge, 235 with 16-gauge and 265 with 18-gauge needles. There were no significant differences between 14-gauge, 16-gauge and 18-gauge needles in rates of specimen inadequacy (0 %, 0.4 % and 1.9 %, respectively) (p = 0.084); surgical discordance (2.6 %, 2.9 % and 3.8 %) (p = 0.76); imaging discordance (0 %, 0 % and 2 %) (p = 1.0); DCIS upgrade (43 %, 43 % and 36 %) (p = 1.00) or high-risk lesion upgrade (38 %, 25 % and 55 %) (p = 0.49). CONCLUSION: There was no statistically significant difference in diagnostic accuracy of US-guided CNB of breast masses performed with 14-gauge, 16-gauge and 18-gauge needles. KEY POINTS: • Percutaneous image-guided breast core needle biopsy (CNB) is the standard of care. • Breast CNB with 14-gauge, 16-gauge and 18-gauge needles has similar diagnostic accuracy. • Smaller gauge needles can be confidently used for ultrasound-guided breast CNB.

Phase I biomarker modulation study of atorvastatin in women at increased risk for breast cancer.

Selective estrogen receptor modulators (SERMs), tamoxifen, and raloxifene that reduce the risk of breast cancer are limited to only estrogen receptor-positive (ER(+)) breast cancer. In addition, patient acceptance of SERMs is low due to toxicity and intolerability. New agents with improved toxicity profile that reduce risk of ER-negative breast cancer are urgently needed. Observational studies show that statins can reduce breast cancer incidence and recurrence. The objective of this prospective short-term prevention study was to evaluate the effect of a lipophilic statin, atorvastatin, on biomarkers in breast tissue and serum of women at increased risk. Eligible participants included women with previous history of carcinoma in situ, or atypical hyperplasia, or 5 year breast cancer projected Gail risk >1.67 %, or lifetime breast cancer risk >20 % calculated by models including Claus, Tyrer-Cuzick, Boadicea, or BRCAPRO. Patients underwent baseline fine needle aspiration (FNA) of the breast, blood collection for biomarker analysis, and were randomized to either no treatment or atorvastatin at 10, 20, or 40 mg/day dose for 3 months. At 3 months, blood collection and breast FNA were repeated. Biomarkers included C-reactive protein (CRP), lipid profile, atorvastatin, and its metabolites, Ki-67, bcl-2, EGFR, and pEGFR. Baseline genotype for 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR) was also measured. Among 60 patients evaluated, a significant reduction in serum CRP, cholesterol and low-density lipoprotein (LDL), and increase in atorvastatin metabolites in serum and breast FNAs was demonstrated. No changes were observed in other tissue biomarkers. This study shows that atorvastatin and its metabolites are detectable in breast samples and may lower serum CRP among women without hyperlipidemia.

Accuracy of EasyChip HPV blot genotyping assay to detect high-risk HPV genotypes in SurePath Papanicolaou specimens.

INTRODUCTION: EasyChip HPV blot is a human papillomavirus (HPV) genotyping assay that can be potentially used for HPV assay validation or clinical HPV research. To evaluate its genotyping accuracy, we compared EasyChip HPV blot with quantitative real-time polymerase chain reaction (qRT-PCR)/type-specific PCR assays in the detection of 8 high-risk HPV genotypes. MATERIALS AND METHODS: Archival SurePath Papanicolaou specimens with abnormal results and follow-up biopsy (n = 154) were selected retrospectively for HPV genotyping by EasyChip HPV blot. To determine the accuracy of the assay, qRT-PCR and type-specific PCR also were performed and results for 8 high-risk HPV genotypes were compared (HPV16, 18, 31, 33, 35, 45, 52, and 58). RESULTS: A total of 95 Papanicolaou specimens were qualified for data analysis. Concordance between EasyChip HPV blot and qRT-PCR/type-specific PCR assays was high, with a very good agreement for the 8 high-risk HPV genotypes (95%; kappa value: 0.894, 95% CI: 0.805-0.984) and for HPV16 and HPV18 (96%; kappa value: 0.899, 95% CI: 0.802-0.996). HPV16 was the most frequent HPV genotype by EasyChip HPV blot. The odds ratio of HPV16/18 for high-grade cervical intraepithelial neoplasia was 11.25 (95% CI: 3.93-32.31). CONCLUSIONS: EasyChip HPV blot is a reliable HPV genotyping assay that can be used for HPV assay validation or clinical HPV studies.

Prognosis of gastric adenocarcinoma patients with various burdens of peritoneal metastases.

BACKGROUND: Peritoneal metastases (PM) in patients with gastric adenocarcinoma (GAC) may be identified by diagnostic laparoscopy (DL) or imaging (I). Although prognosis is poor, some patients have excellent outcome. We compared the overall survival (OS) of patients in 3 groups: those with positive cytology (CY+) by DL (DL-CY+), those with gross PM (GPM) by DL (DL-GPM+) and with GPM obvious on I (I-GPM+). METHODS: 146 GAC patients were identified. The Kaplan-Meier analysis, univariate, and multivariate Cox proportional hazards regression models were employed. RESULTS: Patients were primarily men (67%), with good ECOG scores (0-1; 89%), had DL (84%), had poorly differentiated GAC (92%), and had received chemotherapy (89%). The median OS for all patients was 15 months (5% CI, 12.9-18.2 months). The DL-CY+ group had median OS of 22.5 months (95% CI, 15-29.3 months). Patients with I-GPM+ had four times the risk of death than those with DL-CY+ (P < 0.001) and patients with DL-GPM+ had two times the risk of death than those with DL-CY+ (P = 0.001). At 36 months, all DL-GPM+ and I-GPM+ had died but 8 patients with DL-CY+ remained alive. CONCLUSIONS: Some GAC patients with DL-CY+ have long OS; therefore, novel strategies to further prolong their OS are needed.