Publications by authors named "Varadan Sevilimedu"

32 Publications

Does preoperative MRI accurately stratify early-stage HER2 + breast cancer patients to upfront surgery vs neoadjuvant chemotherapy?

Breast Cancer Res Treat 2021 Jul 14. Epub 2021 Jul 14.

Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.

Purpose: HER2 +- amplified breast cancer patients derive benefit from treatment with anti-HER2-targeted therapy. Though adjuvant treatment is based on final pathology, decisions regarding neoadjuvant chemotherapy are made in the preoperative setting with imaging playing a key role in staging. We examined the accuracy of pre-operative imaging in determining pathological tumor size  (pT) in patients undergoing upfront surgery.

Methods: Early (cT1-T2N0) HER2 + breast cancer patients who underwent upfront surgery between 2015 and 2016 were identified from a prospective institutional database. We compared data for both clinical and final pathologic stage. Only those who underwent magnetic resonance imaging (MRI), mammography, and ultrasound in the preoperative setting were included in the analysis. Adjuvant treatment regimens were reviewed.

Results: We identified 87 cT1-2N0 patients with invasive HER2 + breast cancer who underwent upfront surgery. Median age was 52 years (IQR 43, 58) and median tumor size was 1.1 cm (IQR 0.5, 1.6). Fifteen patients (17%) were upstaged to stage II/III based on final pathology. Thirty-seven patients were T1cN0 on final pathology; 8 were cT1a-bN0 preop and 12 had pT overestimated by MRI by an average of 1.5 cm (> 0.5-1.5 cm). Compared to both mammography and MRI, the imaging modality most predictive of pT was ultrasound (p = 0.000072 ultrasound vs mammography and 0.000042 ultrasound vs MRI).

Conclusion: For small HER2 + cN0 tumors undergoing upfront surgery, ultrasound was the imaging modality most predictive of pT. MRI overestimated tumor size in approximately 40% of patients. MRI may not accurately discriminate low-volume tumor burden in the breast and carries the potential of overtreatment in the upfront setting.
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http://dx.doi.org/10.1007/s10549-021-06331-3DOI Listing
July 2021

Postdischarge Nonsteroidal Anti-Inflammatory Drugs Are not Associated with Risk of Hematoma after Lumpectomy and Sentinel Lymph Node Biopsy with Multimodal Analgesia.

Ann Surg Oncol 2021 Jul 10. Epub 2021 Jul 10.

Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are increasingly used in ambulatory breast surgery. The risk of hematoma associated with intraoperative ketorolac is low, but whether concomitant routine discharge with NSAIDs increases the risk of hematoma is unclear.

Methods: We retrospectively identified patients who underwent lumpectomy and sentinel lymph node biopsy (SLNB), and compared the 30-day risk of hematoma between patients discharged with opioids (opioid period: January 2018-August 2018) and patients discharged with NSAIDs with or without opioids (NSAID period: January 2019-April 2020). The association between study period and hematoma risk was assessed using multivariable models. Covariates included intraoperative ketorolac, home aspirin, and race/ethnicity. During the NSAID period, a survey was used to assess analgesic consumption on postoperative days 1-5.

Results: In total, 2724 patients were identified: 858 (31%) in the opioid period and 1866 (69%) in the NSAID period. In the NSAID period, 867 (46%) received NSAIDs and opioids, and 999 (54%) received NSAIDs only. Receipt of intraoperative ketorolac was higher in the NSAID period (78 vs. 64%, P < 0.001). The risks of any hematoma (4.1 vs. 3.6%, P = 0.6) and reoperation for bleeding (0.5 vs. 0.6%, P = 0.8) were similar between groups. Study period was not associated with hematoma risk (odds ratio 0.87, 95% confidence interval 0.56-1.35, P = 0.5). Among survey respondents (41%), nonopioid analgesic consumption did not increase after opioids were removed from the discharge regimen (median, 6 pills/group, P = 0.06).

Conclusions: NSAIDs are associated with a low risk of hematoma after lumpectomy and SLNB, and should be prescribed instead of opioids, unless contraindicated.
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http://dx.doi.org/10.1245/s10434-021-10446-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272604PMC
July 2021

PD-L1 Expression in Metaplastic Breast Carcinoma Using the PD-L1 SP142 Assay and Concordance Among PD-L1 Immunohistochemical Assays.

Am J Surg Pathol 2021 Jun 10. Epub 2021 Jun 10.

Departments of Pathology Medicine Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.

Immunotherapy for the treatment of programmed death-ligand 1 (PD-L1) positive locally advanced or metastatic triple negative breast cancer may benefit patients with metaplastic breast cancer (MpBC). Previous study of PD-L1 in MpBC scored tumor cells (TCs), different from Food and Drug Administration-approved scoring methods. We sought to define PD-L1 expression in MpBCs and to evaluate concordance of 3 PD-L1 assays. Primary, treatment naive MpBC treated at our Center from 1998 to 2019 were identified. PD-L1 expression was assessed using SP142, E1L3n, and 73-10. We evaluated PD-L1 expression on tumor infiltrating immune cells (IC) and also in TCs. For each assay, we scored PD-L1 expression using ≥1% IC expression according to the IMpassion130 trial criteria and using combined positive score (CPS) ≥10 according to the KEYNOTE-355 trial cutoff. A total of 42 MpBCs were identified. Most MpBC had PD-L1 positivity in ≥1% IC with all 3 assays (95%, 95%, 86%) in contrast to a maximum 71% with a CPS ≥10. PD-L1 IC expression was comparable between the SP142 and 73-10 assays and was lowest with E1L3n. PD-L1 TC expression was lowest using SP142. The overall concordance for IC scoring was 88% while 62% had concordant CPS. For each assay, the results of the 2 scoring algorithms were not interchangeable. The SP142 assay showed distinct expression patterns between IC (granular, dot-like) and TC (membranous) while 73-10 and E1L3n showed membranous and/or cytoplasmic expression in both IC and TC. Most MpBC in our cohort were positive for PD-L1 indicating eligibility for anti-PD-L1/programmed death-1 immunotherapy.
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http://dx.doi.org/10.1097/PAS.0000000000001760DOI Listing
June 2021

Radiomics and Machine Learning with Multiparametric Breast MRI for Improved Diagnostic Accuracy in Breast Cancer Diagnosis.

Diagnostics (Basel) 2021 May 21;11(6). Epub 2021 May 21.

Department of Radiology, Breast Imaging Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

The purpose of this multicenter retrospective study was to evaluate radiomics analysis coupled with machine learning (ML) of dynamic contrast-enhanced (DCE) and diffusion-weighted imaging (DWI) radiomics models separately and combined as multiparametric MRI for improved breast cancer detection. Consecutive patients (Memorial Sloan Kettering Cancer Center, January 2018-March 2020; Medical University Vienna, from January 2011-August 2014) with a suspicious enhancing breast tumor on breast MRI categorized as BI-RADS 4 and who subsequently underwent image-guided biopsy were included. In 93 patients (mean age: 49 years ± 12 years; 100% women), there were 104 lesions (mean size: 22.8 mm; range: 7-99 mm), 46 malignant and 58 benign. Radiomics features were calculated. Subsequently, the five most significant features were fitted into multivariable modeling to produce a robust ML model for discriminating between benign and malignant lesions. A medium Gaussian support vector machine (SVM) model with five-fold cross validation was developed for each modality. A model based on DWI-extracted features achieved an AUC of 0.79 (95% CI: 0.70-0.88), whereas a model based on DCE-extracted features yielded an AUC of 0.83 (95% CI: 0.75-0.91). A multiparametric radiomics model combining DCE- and DWI-extracted features showed the best AUC (0.85; 95% CI: 0.77-0.92) and diagnostic accuracy (81.7%; 95% CI: 73.0-88.6). In conclusion, radiomics analysis coupled with ML of multiparametric MRI allows an improved evaluation of suspicious enhancing breast tumors recommended for biopsy on clinical breast MRI, facilitating accurate breast cancer diagnosis while reducing unnecessary benign breast biopsies.
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http://dx.doi.org/10.3390/diagnostics11060919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223779PMC
May 2021

Reconstruction in Women with T4 Breast Cancer after Neoadjuvant Chemotherapy: When Is It Safe?

J Am Coll Surg 2021 May 3. Epub 2021 May 3.

Breast Service. Electronic address:

Background: Despite limited evidence regarding its safety, immediate reconstruction (IR) is increasingly offered to women with T4 breast cancer. We compared outcomes after IR, delayed reconstruction (DR), and no reconstruction (NR) in patients treated with neoadjuvant chemotherapy (NAC) and postmastectomy radiation therapy (PMRT) for T4 disease.

Study Design: We retrospectively identified consecutive women with T4 tumors treated with trimodality therapy from January 2007 through December 2019. Clinicopathologic characteristics, complications requiring reoperation, time to PMRT, and recurrence patterns were compared. The cumulative incidence of local recurrence (LR) was estimated using Kaplan-Meier methods.

Results: Of the 269 women identified, the median (IQR) age was 52 (45-62) years; 164 women (61%) had T4d disease. Forty-five women (17%) had IR, 41 (15%) had DR, and 183 (68%) had NR. IR was independently associated with T4a-c disease (odds ratio [OR], 5.75; 95% CI, 2.57-12.87; p < 0.001) and younger age (OR 0.91; 95% CI, 0.86-0.94; p < 0.001). The risk of complications after IR was 22% overall and 46% in T4d patients (6/13), compared with 4.4% overall for NR and 7.3% for DR (p < 0.001). IR was associated with >8-week interval to PMRT (p < 0.001). At a median (range) follow-up of 4.2 (0.2-13) years, the median time to first recurrence was 18 months and was similar between groups (p = 0.13). The cumulative incidence of LR was 16% for T4d disease and 2.2% for T4a-c disease (p < 0.001).

Conclusions: After IR, women with T4 tumors, particularly T4d disease, experienced delayed initiation of adjuvant treatment and substantial morbidity, suggesting that an interval of >18 months between mastectomy and reconstruction is advisable.
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http://dx.doi.org/10.1016/j.jamcollsurg.2021.04.016DOI Listing
May 2021

Palpable Adenopathy Does Not Indicate High-Volume Axillary Nodal Disease in Hormone Receptor-Positive Breast Cancer.

Ann Surg Oncol 2021 Apr 19. Epub 2021 Apr 19.

Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: Axillary metastases in the form of palpable adenopathy indicate the need for neoadjuvant chemotherapy or axillary lymph node dissection (ALND). Patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) disease infrequently have nodal pathologic complete response to neoadjuvant chemotherapy and often require ALND. Sentinel lymph node biopsy is an accepted treatment for patients with two or fewer non-palpable nodal metastases who are undergoing breast conservation. The proportion of patients with HR+/HER2- disease with palpable adenopathy and two or fewer nodal metastases is unknown.

Methods: Patients with cT1-T3N1 HR+/HER2- disease with palpable adenopathy were identified from a prospective database. Patients who underwent mastectomy or breast-conserving therapy with ALND were included in this study, whereas patients who received neoadjuvant chemotherapy were excluded. Clinicopathologic characteristics were compared between patients with two or fewer or more than two positive nodes on ALND.

Results: Of 180 patients included, 78 (43%) had two or fewer positive nodes on ALND, including 40/72 patients (56%) who underwent lumpectomy. On univariate analysis, cT1 tumor, unifocal tumor, only one palpable node, and two or fewer suspicious nodes on ultrasound were associated with two or fewer positive nodes on ALND. On multivariable analysis, number of suspicious nodes on ultrasound and cT stage were independently associated with two or fewer positive nodes on ALND.

Conclusions: A substantial minority of patients with cT1-3N1 HR+/HER2- disease with palpable adenopathy had two or fewer positive nodes on ALND. Standard clinicopathologic features and ultrasound findings can help identify candidates for upfront sentinel lymph node biopsy as a strategy to avoid ALND. Prospective studies evaluating this approach are warranted.
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http://dx.doi.org/10.1245/s10434-021-09943-7DOI Listing
April 2021

Tumor-Nipple Distance of ≥ 1 cm Predicts Negative Nipple Pathology After Neoadjuvant Chemotherapy.

Ann Surg Oncol 2021 Apr 17. Epub 2021 Apr 17.

Breast Service, Department of Surgery, Breast and Imaging Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: As neoadjuvant chemotherapy (NAC) for breast cancer has become more widely used, so has nipple-sparing mastectomy. A common criterion for eligibility is a 1 cm tumor-to-nipple distance (TND), but its suitability after NAC is unclear. In this study, we examined factors predictive of negative nipple pathologic status (NS-) in women undergoing total mastectomy after NAC.

Methods: Women with invasive breast cancer treated with NAC and total mastectomy from August 2014 to April 2018 at our institution were retrospectively identified. Following review of pre- and post-NAC magnetic resonance imaging (MRI) and mammograms, the association of clinicopathologic and imaging variables with NS- was examined and the accuracy of 1 cm TND on imaging for predicting NS- was determined.

Results: Among 175 women undergoing 179 mastectomies, 74% of tumors were cT1-T2 and 67% were cN+ on pre-NAC staging; 10% (18/179) had invasive or in situ carcinoma in the nipple on final pathology. On multivariable analysis, after adjusting for age, grade, and tumor stage, three factors, namely number of positive nodes, pre-NAC nipple-areolar complex retraction, and decreasing TND, were significant predictors of nipple involvement (p < 0.05). The likelihood of NS- was higher with increasing TND on pre- and post-NAC imaging (p < 0.05). TND ≥ 1 cm predicted NS- in 97% and 95% of breasts on pre- and post-NAC imaging, respectively.

Conclusions: Increasing TND was associated with a higher likelihood of NS-. A TND ≥ 1 cm on pre- or post-NAC imaging is highly predictive of NS- and could be used to determine eligibility for nipple-sparing mastectomy after NAC.
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http://dx.doi.org/10.1245/s10434-021-09902-2DOI Listing
April 2021

Fat Composition Measured by Proton Spectroscopy: A Breast Cancer Tumor Marker?

Diagnostics (Basel) 2021 Mar 21;11(3). Epub 2021 Mar 21.

Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.

Altered metabolism including lipids is an emerging hallmark of breast cancer. The purpose of this study was to investigate if breast cancers exhibit different magnetic resonance spectroscopy (MRS)-based lipid composition than normal fibroglandular tissue (FGT). MRS spectra, using the stimulated echo acquisition mode sequence, were collected with a 3T scanner from patients with suspicious lesions and contralateral normal tissue. Fat peaks at 1.3 + 1.6 ppm (L13 + L16), 2.1 + 2.3 ppm (L21 + L23), 2.8 ppm (L28), 4.1 + 4.3 ppm (L41 + L43), and 5.2 + 5.3 ppm (L52 + L53) were quantified using LCModel software. The saturation index (SI), number of double bods (NBD), mono and polyunsaturated fatty acids (MUFA and PUFA), and mean chain length (MCL) were also computed. Results showed that mean concentrations of all lipid metabolites and PUFA were significantly lower in tumors compared with that of normal FGT ( ≤ 0.002 and 0.04, respectively). The measure best separating normal and tumor tissues after adjusting with multivariable analysis was L21 + L23, which yielded an area under the curve of 0.87 (95% CI: 0.75-0.98). Similar results were obtained between HER2 positive versus HER2 negative tumors. Hence, MRS-based lipid measurements may serve as independent variables in a multivariate approach to increase the specificity of breast cancer characterization.
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http://dx.doi.org/10.3390/diagnostics11030564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004005PMC
March 2021

Contrast-Enhanced Digital Mammography Screening for Intermediate-Risk Women With a History of Lobular Neoplasia.

AJR Am J Roentgenol 2021 06 31;216(6):1486-1491. Epub 2021 Mar 31.

Department of Radiology, Memorial Sloan Kettering Cancer Center, Breast Imaging Service, 300 E 66th St, New York, NY 10065.

The objective of this study was to assess to the role of contrast-enhanced digital mammography (CEDM) as a screening tool in women at intermediate risk for developing breast cancer due to a personal history of lobular neoplasia without additional risk factors. In this institutional review board-approved, observational, retrospective study, we reviewed our radiology department database to identify patients with a personal history of breast biopsy yielding lobular neoplasia who underwent screening CEDM at our institution between December 2012 and February 2019. A total of 132 women who underwent 306 CEDM examinations were included. All CEDM examinations were interpreted by dedicated breast imaging radiologists in conjunction with a review of the patient's clinical history and available prior breast imaging. In statistical analysis, sensitivity, specificity, NPV, positive likelihood ratio, and accuracy of CEDM in detecting cancer were determined, with pathology or 12-month imaging follow-up serving as the reference standard. CEDM detected cancer in six patients and showed an overall sensitivity of 100%, specificity of 88% (95% CI, 84-92%), NPV of 100%, and accuracy of 88% (95% CI, 84-92%). The positive likelihood ratio of 8.33 suggested that CEDM findings are 8.3 times more likely to be positive in an individual with breast cancer when compared with an individual without the disease. CEDM shows promise as a breast cancer screening examination in patients with a personal history of lobular neoplasia. Continued investigation with a larger patient population is needed to determine the true sensitivity and positive predictive value of CEDM for these patients.
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http://dx.doi.org/10.2214/AJR.20.23480DOI Listing
June 2021

Patterns of invasive recurrence among patients originally treated for ductal carcinoma in situ by breast-conserving surgery versus mastectomy.

Breast Cancer Res Treat 2021 Apr 6;186(3):617-624. Epub 2021 Mar 6.

Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Purpose: Local recurrence after treatment of ductal carcinoma in situ (DCIS) with breast-conserving surgery (BCS) is more common than after mastectomy, but it is unclear if patterns of invasive recurrence vary by initial surgical therapy. Among patients with invasive recurrence after treatment for DCIS, we compared patterns of first recurrence between those originally treated with BCS vs. mastectomy.

Methods: From 2000 to 2016, women with an invasive recurrence occurring ≥ 6 months after initial treatment for DCIS were retrospectively identified. Clinicopathologic features and adjuvant treatment of the initial DCIS, as well as characteristics of first invasive recurrences, were compared between patients who had undergone BCS vs. mastectomy.

Results: 452 patients with an invasive recurrence after surgery for DCIS were identified: 367 patients (81%) had initially undergone BCS and 85 patients (19%) mastectomy. Patients originally treated with mastectomy were younger and were more likely to have had high grade, necrosis, and multifocal or multicentric DCIS (p < 0.001) compared with the BCS group. A higher proportion of invasive recurrences were local after BCS (93%; 343/367), whereas 88% (75/85) of recurrences after mastectomy were regional or distant (p < 0.001). The median time to first invasive recurrence was not different between surgical groups (BCS: 6.4 years vs. mastectomy: 5.5 years; p = 0.12).

Conclusions: Among women who experienced a first invasive recurrence after treatment for DCIS, those who had originally undergone mastectomy more commonly presented with advanced disease compared to those treated with BCS, likely related to the absence of the breast and the higher risk profile of their initial DCIS.
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http://dx.doi.org/10.1007/s10549-021-06129-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019411PMC
April 2021

Reply to: Metaplastic Breast Carcinoma and Other Triple-Negative Subtype Breast Cancers: Which is the Worst?

Ann Surg Oncol 2021 Feb 10. Epub 2021 Feb 10.

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

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http://dx.doi.org/10.1245/s10434-021-09679-4DOI Listing
February 2021

Breast conservation among older patients with early-stage breast cancer: Locoregional recurrence following adjuvant radiation or hormonal therapy.

Cancer 2021 Jun 26;127(11):1749-1757. Epub 2021 Jan 26.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.

Background: For patients with breast cancer undergoing breast-conserving surgery (BCS), adjuvant radiation (RT) and hormonal therapy (HT) reduce the risk of locoregional recurrence (LRR). Although several studies have evaluated adjuvant HT ± RT, the outcomes of HT versus RT monotherapy remain less clear. In this study, the risk of LRR is characterized among older patients with early-stage breast cancer following adjuvant RT alone, HT alone, neither, or both.

Methods: This study included female patients from the Memorial Sloan Kettering Cancer Center (New York, New York) who were aged ≥65 years with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) T1N0 breast cancer treated with BCS. The primary endpoint was time to LRR evaluated by Cox regression analysis.

Results: There were 888 women evaluated with a median age of 71 years (range, 65-100 years) and median follow-up of 4.9 years (range, 0.0-9.5 years). There were 27 LRR events (3.0%). Five-year LRR was 11% for those receiving no adjuvant treatment, 3% for HT alone, 4% for RT alone, and 1% for HT and RT. LRR rates were significantly different between the groups (P < .001). Compared with neither HT nor RT, HT or RT monotherapy each yielded similar LRR reductions: HT alone (HR, 0.27; 95% CI, 0.10-0.68; P = .006) and RT alone (HR, 0.32; 95% CI, 0.11-0.92; P = .034). Distant recurrence and breast cancer-specific survival rates did not significantly differ between groups.

Conclusions: LRR risk following BCS is low among women aged ≥65 years with T1N0, ER+/HER2- breast cancer. Adjuvant RT and HT monotherapy each similarly reduce this risk; the combination yields a marginal improvement. Further study is needed to elucidate whether appropriate patients may feasibly receive adjuvant RT monotherapy versus the current standards of HT monotherapy or combined RT/HT.
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http://dx.doi.org/10.1002/cncr.33422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113065PMC
June 2021

Accuracy of Magnetic Resonance Imaging-Guided Biopsy to Verify Breast Cancer Pathologic Complete Response After Neoadjuvant Chemotherapy: A Nonrandomized Controlled Trial.

JAMA Netw Open 2021 01 4;4(1):e2034045. Epub 2021 Jan 4.

Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.

Importance: After neoadjuvant chemotherapy (NAC), pathologic complete response (pCR) is an optimal outcome and a surrogate end point for improved disease-free and overall survival. To date, surgical resection remains the only reliable method for diagnosing pCR.

Objective: To evaluate the accuracy of magnetic resonance imaging (MRI)-guided biopsy for diagnosing a pCR after NAC compared with reference-standard surgical resection.

Design, Setting, And Participants: Single-arm, phase 1, nonrandomized controlled trial in a single tertiary care cancer center from September 26, 2017, to July 29, 2019. The median follow-up was 1.26 years (interquartile range, 0.85-1.59 years). Data analysis was performed in November 2019. Eligible patients had (1) stage IA to IIIC biopsy-proven operable invasive breast cancer; (2) standard-of-care NAC; (3) MRI before and after NAC, with imaging complete response defined as no residual enhancement on post-NAC MRI; and (4) definitive surgery. Patients were excluded if they were younger than 18 years, had a medical reason precluding study participation, or had a prior history of breast cancer.

Interventions: Post-NAC MRI-guided biopsy without the use of intravenous contrast of the tumor bed before definitive surgery.

Main Outcomes And Measures: The primary end point was the negative predictive value of MRI-guided biopsy, with true-negative defined as negative results of the biopsy (ie, no residual cancer) corresponding to a surgical pCR. Accuracy, sensitivity, positive predictive value, and specificity were also calculated. Two clinical definitions of pCR were independently evaluated: definition 1 was no residual invasive cancer; definition 2, no residual invasive or in situ cancer.

Results: Twenty of 23 patients (87%) had evaluable data (median [interquartile range] age, 51.5 [39.0-57.5] years; 20 women [100%]; 13 White patients [65%]). Of the 20 patients, pre-NAC median tumor size on MRI was 3.0 cm (interquartile range, 2.0-5.0 cm). Nineteen of 20 patients (95%) had invasive ductal carcinoma; 15 of 20 (75%) had stage II cancer; 11 of 20 (55%) had ERBB2 (formerly HER2 or HER2/neu)-positive cancer; and 6 of 20 (30%) had triple-negative cancer. Surgical pathology demonstrated a pCR in 13 of 20 (65%) patients and no pCR in 7 of 20 patients (35%) when pCR definition 1 was used. Results of MRI-guided biopsy had a negative predictive value of 92.8% (95% CI, 66.2%-99.8%), with accuracy of 95% (95% CI, 75.1%-99.9%), sensitivity of 85.8% (95% CI, 42.0%-99.6%), positive predictive value of 100%, and specificity of 100% for pCR definition 1. Only 1 patient had a false-negative MRI-guided biopsy result (surgical pathology showed <0.02 cm of residual invasive cancer).

Conclusions And Relevance: This study's results suggest that the accuracy of MRI-guided biopsy to diagnose a post-NAC pCR approaches that of reference-standard surgical resection. MRI-guided biopsy may be a viable alternative to surgical resection for this population after NAC, which supports the need for further investigation.

Trial Registration: ClinicalTrials.gov Identifier: NCT03289195.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.34045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811182PMC
January 2021

Management of ipsilateral breast tumor recurrence following breast conservation surgery: a comparative study of re-conservation vs mastectomy.

Breast Cancer Res Treat 2021 May 12;187(1):105-112. Epub 2021 Jan 12.

Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: Breast conservation therapy (BCT) is well established for the management of primary operable breast cancer, with oncologic outcomes comparable to those of mastectomy. It remains unclear whether re-conservation therapy (RCT) is suitable for those patients who develop ipsilateral breast tumor recurrence (IBTR), for whom mastectomy is generally recommended.

Methods: We identified women who underwent BCT for invasive or ductal carcinoma in situ and developed IBTR as a first event, comparing the pattern of subsequent events and survival for those treated by RCT versus mastectomy.

Results: Of 16,968 patents who had BCT, 322 (1.9%) developed an isolated IBTR as a first event between 1999 and 2019. 130 (40%) had RCT and 192 (60%) mastectomy. Compared to mastectomy, the RCT patients were older (66 vs 53, < 0.001), had a longer disease-free interval (DFI: 5.8 vs 2.7 years (p < 0.001)), were less likely to have received RT (p < 0.001), endocrine therapy (ET) (p < 0.005) or combined RT/ET (< 0.001) as initial treatment, but the characteristics of their initial primary cancers and of their IBTR were comparable. At a median follow-up of 10.7 years following initial BCT and 6.5 years following IBTR, there were no differences in BCSS or OS between RCT and mastectomy.

Conclusion: For BCT patients who developed IBTR as a first event, we observed comparable BCSS and OS from time of initial treatment and from time of IBTR, whether treated by RCT or mastectomy. These results support wider consideration of RCT in the management of IBTR, especially in the setting of older age and longer DFI.
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http://dx.doi.org/10.1007/s10549-020-06080-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068641PMC
May 2021

Survival Outcomes for Metaplastic Breast Cancer Differ by Histologic Subtype.

Ann Surg Oncol 2021 Aug 2;28(8):4245-4253. Epub 2021 Jan 2.

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: Metaplastic breast carcinoma (MBC) is a rare, aggressive subtype of breast cancer associated with poorer overall survival than other triple-negative breast cancers. This study sought to compare survival outcomes among histologic subtypes of MBC with those of non-metaplastic triple-negative breast cancer.

Methods: Clinicopathologic and treatment data for all patients with non-metastatic, pure MBC undergoing surgery from 1995 to 2017 and for a large cohort of patients with other types of triple-negative breast cancer during that period were collected from an institutional database. The MBC tumors were classified as having squamous, spindle, heterologous mesenchymal, or mixed histology. Survival outcomes were compared using the Kaplan-Meier method.

Results: Of 132 MBC patients, those with heterologous mesenchymal MBC (n = 45) had the best 5-year overall and breast cancer-specific survival (BCSS, 88%; 95% confidence interval [CI], 0.78-0.99), whereas those with squamous MBC had the worst survival (BCSS, 56%; 95% CI, 0.32-0.79). Overall survival, BCSS, and recurrence-free survival were worse for the patients with MBC than for the patients who had non-MBC triple-negative breast cancer, with a clinicopathologically adjusted recurrence hazard ratio of 2.4 (95% CI, 1.6-3.3; p < 0.001). Of the 10 MBC patients who received neoadjuvant chemotherapy, 4 progressed while receiving treatment, and 3 had no response.

Conclusions: Metaplastic breast carcinoma is associated with worse survival than other triple-negative breast cancers. The heterologous mesenchymal subtype is associated with the best survival, whereas the squamous subtype is associated with the worst survival. These data call for research to identify therapies tailored to MBC's unique biology.
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http://dx.doi.org/10.1245/s10434-020-09430-5DOI Listing
August 2021

Pharmacokinetic Analysis of Dynamic Contrast-Enhanced Magnetic Resonance Imaging at 7T for Breast Cancer Diagnosis and Characterization.

Cancers (Basel) 2020 Dec 14;12(12). Epub 2020 Dec 14.

Breast Imaging Service, Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY 10065, USA.

The purpose of this study was to investigate whether ultra-high-field dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the breast at 7T using quantitative pharmacokinetic (PK) analysis can differentiate between benign and malignant breast tumors for improved breast cancer diagnosis and to predict molecular subtypes, histologic grade, and proliferation rate in breast cancer. In this prospective study, 37 patients with 43 lesions suspicious on mammography or ultrasound underwent bilateral DCE-MRI of the breast at 7T. PK parameters (K, k, V) were evaluated with two region of interest (ROI) approaches (2D whole-tumor ROI or 2D 10 mm standardized ROI) manually drawn by two readers (senior reader, R1, and R2) independently. Histopathology served as the reference standard. PK parameters differentiated benign and malignant lesions (n = 16, 27, respectively) with good accuracy (AUCs = 0.655-0.762). The addition of quantitative PK analysis to subjective BI-RADS classification improved breast cancer detection from 88.4% to 97.7% for R1 and 86.04% to 97.67% for R2. Different ROI approaches did not influence diagnostic accuracy for both readers. Except for K for whole-tumor ROI for R2, none of the PK parameters were valuable to predict molecular subtypes, histologic grade, or proliferation rate in breast cancer. In conclusion, PK-enhanced BI-RADS is promising for the noninvasive differentiation of benign and malignant breast tumors.
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http://dx.doi.org/10.3390/cancers12123763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765071PMC
December 2020

Contrast-Enhanced Mammography for Screening Women after Breast Conserving Surgery.

Cancers (Basel) 2020 Nov 24;12(12). Epub 2020 Nov 24.

Department of Radiology, Breast Imaging Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

To investigate the value of contrast-enhanced mammography (CEM) compared to full-field digital mammography (FFDM) in screening breast cancer patients after breast-conserving surgery (BCS), this Health Insurance Portability and Accountability Act-compliant, institutional review board-approved retrospective, single-institution study included 971 CEM exams in 541 asymptomatic patients treated with BCS who underwent screening CEM between January 2013 and November 2018. Histopathology, or at least a one-year follow-up, was used as the standard of reference. Twenty-one of 541 patients (3.9%) were diagnosed with ipsi- or contralateral breast cancer: six (28.6%) cancers were seen with low-energy images (equivalent to FFDM), an additional nine (42.9%) cancers were detected only on iodine (contrast-enhanced) images, and six interval cancers were identified within 365 days of a negative screening CEM. Of the 10 ipsilateral cancers detected on CEM, four were detected on low-energy images (40%). Of the five contralateral cancers detected on CEM, two were detected on low-energy images (40%). Overall, the cancer detection rate (CDR) for CEM was 15.4/1000 (15/971), and the positive predictive value (PPV3) of the biopsies performed was 42.9% (15/35). For findings seen on low-energy images, with or without contrast, the CDR was 6.2/1000 (6/971), and the PPV3 of the biopsies performed was 37.5% (6/16). In the post-BCS screening setting, CEM has a higher CDR than FFDM.
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http://dx.doi.org/10.3390/cancers12123495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760311PMC
November 2020

Continuation phase treatment outcomes for switching, combining, or augmenting strategies for treatment-resistant major depressive disorder: A VAST-D report.

Depress Anxiety 2021 02 22;38(2):185-195. Epub 2020 Nov 22.

VA Connecticut Healthcare System, West Haven, Connecticut, USA.

Background: This secondary analysis of the VA Augmentation and Switching Treatments for Depression study compared the continuation phase treatment outcomes of three commonly used second-step treatment strategies following at least one prior failed medication treatment attempt.

Methods: In total, 1522 outpatients with MDD were randomized to switching to bupropion-SR (S-BUP), combining with bupropion-SR (C-BUP), or augmenting with aripiprazole (A-ARI). Following 12 weeks of acute phase treatment, 725 entered the 24-week continuation treatment phase. Depressive symptom severity, relapse, "emergent" remission, anxiety, suicidal ideation, quality of life, health status, and side effects were compared.

Results: We did not find clinically significant differential treatment effects with the exception that A-ARI was associated with less anxiety than S-BUP or C-BUP. Participants who entered continuation treatment as remitters had milder depressive symptom severity and lower relapse rates than those not in remission; they also experienced more improvement on most other outcomes. A-ARI was associated with less anxiety, insomnia, and dry mouth but more somnolence, extrapyramidal effects, akathisia, abnormal laboratory values, and appetite and weight gain.

Conclusions: Continuation treatment is a dynamic period. Regardless of the treatment, participants who entered continuation treatment at Week 12 in full remission continued to have better outcomes over the subsequent 24 weeks than those who were not in remission at the start of the continuation phase.
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http://dx.doi.org/10.1002/da.23114DOI Listing
February 2021

How Effective is Neoadjuvant Endocrine Therapy (NET) in Downstaging the Axilla and Achieving Breast-Conserving Surgery?

Ann Surg Oncol 2020 Nov 24;27(12):4702-4710. Epub 2020 Aug 24.

Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: Neoadjuvant endocrine therapy (NET) is effective in downstaging large hormone receptor-positive (HR+) breast cancers and increasing rates of breast-conserving surgery (BCS), but data regarding nodal pathologic complete response (pCR) are sparse. We reported nodal and breast downstaging rates with NET, and compared axillary response rates following NET and neoadjuvant chemotherapy (NAC).

Methods: Consecutive stage I-III breast cancer patients treated with NET and surgery from January 2009 to December 2019 were identified from a prospectively maintained database. Nodal pCR rates were compared between biopsy-proven node-positive patients treated with NET, and HR+/HER2- patients treated with NAC from November 2013 to July 2019.

Results: 127 cancers treated with NET and 338 with NAC were included. NET recipients were older, more likely to have lobular and lower-grade tumors, and higher HR expression. With NET, the nodal pCR rate was 11% (4/38) of biopsy-proven cases, and the breast pCR rate was 1.6% (2/126). Nodal-dowstaging rates with NET and NAC were not significantly different (11% vs 18%; P = 0.37). Patients achieving nodal pCR with NET versus NAC were older (median age 70 vs 50, P = 0.004) and had greater progesterone receptor (PR) expression (85% vs 13%, P = 0.031), respectively. Of patients not candidates for BCS due to a large tumor relative to breast size, 36/47 (77%) became BCS-eligible with NET (median PR expression 55% vs 5% in those remaining ineligible, P < 0.05).

Conclusion: Although nodal pCR is more frequent than breast pCR, NET is more likely to de-escalate breast surgery than axillary surgery. However, with a nodal pCR rate of 11%, NET remains an option for downstaging node-positive patients without clear indications for NAC.
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http://dx.doi.org/10.1245/s10434-020-08888-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554166PMC
November 2020

MRI background parenchymal enhancement, fibroglandular tissue, and mammographic breast density in patients with invasive lobular breast cancer on adjuvant endocrine hormonal treatment: associations with survival.

Breast Cancer Res 2020 08 20;22(1):93. Epub 2020 Aug 20.

Department of Radiology, Breast Imaging Service, Memorial Sloan Kettering Cancer Center, 300 E 66th Street, New York, NY, 10065, USA.

Background: To investigate if baseline and/or changes in contralateral background parenchymal enhancement (BPE) and fibroglandular tissue (FGT) measured on magnetic resonance imaging (MRI) and mammographic breast density (MD) can be used as imaging biomarkers for overall and recurrence-free survival in patients with invasive lobular carcinomas (ILCs) undergoing adjuvant endocrine treatment.

Methods: Women who fulfilled the following inclusion criteria were included in this retrospective HIPAA-compliant IRB-approved study: unilateral ILC, pre-treatment breast MRI and/or mammography from 2000 to 2010, adjuvant endocrine treatment, follow-up MRI, and/or mammography 1-2 years after treatment onset. BPE, FGT, and mammographic MD of the contralateral breast were independently graded by four dedicated breast radiologists according to BI-RADS. Associations between the baseline levels and change in levels of BPE, FGT, and MD with overall survival and recurrence-free survival were assessed using Kaplan-Meier survival curves and Cox regression analysis.

Results: Two hundred ninety-eight patients (average age = 54.1 years, range = 31-79) fulfilled the inclusion criteria. The average follow-up duration was 11.8 years (range = 2-19). Baseline and change in levels of BPE, FGT, and MD were not significantly associated with recurrence-free or overall survival. Recurrence-free and overall survival were affected by histological subtype (p < 0.0001), number of metastatic axillary lymph nodes (p < 0.0001), age (p = 0.01), and adjuvant endocrine treatment duration (p < 0.001).

Conclusions: Qualitative evaluation of BPE, FGT, and mammographic MD changes cannot predict which patients are more likely to benefit from adjuvant endocrine treatment.
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http://dx.doi.org/10.1186/s13058-020-01329-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441557PMC
August 2020

Diagnostic value of diffusion-weighted imaging with synthetic b-values in breast tumors: comparison with dynamic contrast-enhanced and multiparametric MRI.

Eur Radiol 2021 Jan 11;31(1):356-367. Epub 2020 Aug 11.

Department of Radiology, Breast Imaging Service, Memorial Sloan Kettering Cancer Center, 300 E 66th Street, New York, NY, 10065, USA.

Objectives: To assess DWI for tumor visibility and breast cancer detection by the addition of different synthetic b-values.

Methods: Eighty-four consecutive women who underwent a breast-multiparametric-MRI (mpMRI) with enhancing lesions on DCE-MRI (BI-RADS 2-5) were included in this IRB-approved retrospective study from September 2018 to March 2019. Three readers evaluated DW acquired b-800 and synthetic b-1000, b-1200, b-1500, and b-1800 s/mm images for lesion visibility and preferred b-value based on lesion conspicuity. Image quality (1-3 scores) and breast composition (BI-RADS) were also recorded. Diagnostic parameters for DWI were determined using a 1-5 malignancy score based on qualitative imaging parameters (acquired + preferred synthetic b-values) and ADC values. BI-RADS classification was used for DCE-MRI and quantitative ADC values + BI-RADS were used for mpMRI.

Results: Sixty-four malignant (average = 23 mm) and 39 benign (average = 8 mm) lesions were found in 80 women. Although b-800 achieved the best image quality score, synthetic b-values 1200-1500 s/mm were preferred for lesion conspicuity, especially in dense breast. b-800 and synthetic b-1000/b-1200 s/mm values allowed the visualization of 84-90% of cancers visible with DCE-MRI performing better than b-1500/b-1800 s/mm. DWI was more specific (86.3% vs 65.7%, p < 0.001) but less sensitive (62.8% vs 90%, p < 0.001) and accurate (71% vs 80.7%, p = 0.003) than DCE-MRI for breast cancer detection, where mpMRI was the most accurate modality accounting for less false positive cases.

Conclusion: The addition of synthetic b-values enhances tumor conspicuity and could potentially improve tumor visualization particularly in dense breast. However, its supportive role for DWI breast cancer detection is still not definite.

Key Points: • The addition of synthetic b-values (1200-1500 s/mm) to acquired DWI afforded a better lesion conspicuity without increasing acquisition time and was particularly useful in dense breasts. • Despite the use of synthetic b-values, DWI was less sensitive and accurate than DCE-MRI for breast cancer detection. • A multiparametric MRI modality still remains the best approach having the highest accuracy for breast cancer detection and thus reducing the number of unnecessary biopsies.
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http://dx.doi.org/10.1007/s00330-020-07094-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755636PMC
January 2021

Does Use of Neoadjuvant Chemotherapy Affect the Decision to Pursue Fertility Preservation Options in Young Women with Breast Cancer?

Ann Surg Oncol 2020 Nov 7;27(12):4740-4749. Epub 2020 Aug 7.

Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: The American Society of Clinical Oncology guidelines recommend early referral to reproductive endocrinology and infertility (REI) specialists for young women diagnosed with breast cancer. Current practice patterns demonstrate an increased utilization of neoadjuvant chemotherapy (NAC). We evaluated premenopausal women with breast cancer after consultation with a Fertility Nurse Specialist (FNS) and determine factors associated with referral to REI specialists.

Methods: This retrospective review included all premenopausal women diagnosed at our institution with stage 0-III unilateral breast cancers between 2009 and 2015 who completed an FNS consultation. Clinicopathologic features and factors associated with referral to REI after FNS consultation were analyzed.

Results: A total of 334 women were identified. Median age was 35 years (interquartile range 32-38). The majority of women were single (n = 198, 59.3%) and nulliparous (n = 239, 71.6%). REI referrals were common (n = 237, 71.0%). The Breast Surgery service was the most frequent referring service (n = 194, 58.1%), with significantly more REI referrals compared to Breast Medicine and Genetics services (p = 0.002). Nulliparity was associated with REI referral (p < 0.0001). Adjuvant chemotherapy (p = 0.003) was associated with pursuing REI referral, whereas NAC (p < 0.001) was associated with declining REI referral.

Conclusions: Most women elected to consult with an REI specialist, confirming strong interest in fertility preservation among premenopausal women with breast cancer. However, women receiving NAC more frequently declined referral to REI, suggesting that the need to start NAC may influence decisions regarding fertility preservation. With increasing utilization of NAC, our study supports the need for further counseling and education regarding fertility preservation for women undergoing NAC.
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http://dx.doi.org/10.1245/s10434-020-08883-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554118PMC
November 2020

Changing the Default: A Prospective Study of Reducing Discharge Opioid Prescription after Lumpectomy and Sentinel Node Biopsy.

Ann Surg Oncol 2020 Nov 30;27(12):4637-4642. Epub 2020 Jul 30.

Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: Whether routinely prescribed opioids are necessary for pain control after discharge among lumpectomy/sentinel node biopsy (Lump/SLNB) patients is unclear. We hypothesize that Lump/SLNB patients could be discharged without opioids, with a failure rate < 10%. This study prospectively examines outcomes after changing standard discharge prescription from an opioid/non-steroidal anti-inflammatory drug (NSAID) to NSAID/acetaminophen.

Patients And Methods: Standard discharge pain medication orders included opioids in the first 3-month study period and were changed to NSAID/acetaminophen in the second 3-month period. Patient-reported medication consumption and pain scores were collected by post-discharge survey. Frequency of discharge with opioid, NSAID/acetaminophen failure rate, opioid use, and pain scores were examined.

Results: From May to October 2019, 663 patients had Lump/SLNB: 371 in the opioid study period and 292 in the NSAID period. In the opioid period, 92% (342/371) of patients were prescribed an opioid at discharge; of 142 patients who documented opioid use on the survey, 86 (61%) used zero tablets. Among 56 (39%) patients who used opioids, the median number taken by POD 5 was 4. After the change to NSAID/acetaminophen, rates of opioid prescription decreased to 14% (41/292). The NSAID/acetaminophen failure rate was 2% (5/251). Among survey respondents, there was no significant difference in the maximum reported pain scores (POD 1-5) between the opioid period and the NSAID period (p = 0.7).

Conclusions: In Lump/SLNB patients, a change to default discharge with NSAID/acetaminophen resulted in a 78% absolute reduction in opioid prescription, with a failure rate of 2% and no difference in patient-reported pain scores. Most Lump/SLNB patients can be discharged with NSAID/acetaminophen.
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http://dx.doi.org/10.1245/s10434-020-08886-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554186PMC
November 2020

Impact of Concurrent Posttraumatic Stress Disorder on Outcomes of Antipsychotic Augmentation for Major Depressive Disorder With a Prior Failed Treatment: VAST-D Randomized Clinical Trial.

J Clin Psychiatry 2020 06 23;81(4). Epub 2020 Jun 23.

The names of all participants in the VAST-D Study are listed in Supplementary Appendix 1.

Objective: To determine whether concurrent posttraumatic stress disorder (PTSD) should affect whether to augment or switch medications when major depressive disorder (MDD) has not responded to a prior antidepressant trial.

Methods: Patients at 35 Veterans Health Administration medical centers from December 2012 to May 2015 with nonpsychotic MDD (N = 1,522) and a suboptimal response to adequate antidepressant treatment were randomly assigned to 3 "next step" treatments: switching to bupropion, augmenting the current antidepressant with bupropion, and augmenting with the antipsychotic aripiprazole. Blinded ratings with the 16-item Quick Inventory of Depressive Symptomatology-Clinician Rated (QIDS-C₁₆) determined remission and response by 12 weeks and relapse after remission. Survival analyses compared treatment effects in patients with concurrent PTSD diagnosed with the Mini-International Neuropsychiatric Interview (n = 717, 47.1%) and those without PTSD (n = 805, 52.9%).

Results: Patients diagnosed with PTSD showed more severe depressive symptoms at baseline and were less likely to achieve either remission or response by 12 weeks. Augmentation with aripiprazole was associated with greater likelihood of achieving response (68.4%) than switching to bupropion (57.7%) in patients with PTSD (relative risk [RR] = 1.26; 95% CI, 1.01-1.59) as well as in patients without PTSD (RR = 1.29; 95% CI, 1.05-1.97) (78.9% response with aripiprazole augmentation vs 66.9% with switching to bupropion). Treatment comparisons with the group receiving augmentation with bupropion were not significant. There was no significant interaction between treatment group and PTSD on remission (P = .70), response (P = .98), or relapse (P = .15).

Conclusions: Although PTSD was associated with poorer overall outcomes, the presence of concurrent PTSD among Veterans in this trial did not affect the comparative effectiveness of medications on response, remission, or relapse after initial remission.

Trial Registration: ClinicalTrials.gov identifier: NCT01421342.
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http://dx.doi.org/10.4088/JCP.19m13038DOI Listing
June 2020

How Often Does Modern Neoadjuvant Chemotherapy Downstage Patients to Breast-Conserving Surgery?

Ann Surg Oncol 2021 Jan 8;28(1):287-294. Epub 2020 Jun 8.

Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: Neoadjuvant chemotherapy (NAC) has been proven to increase breast-conserving surgery (BCS) rates, but data are limited on conversion rates from BCS-ineligible (BCSi) to BCS-eligible (BCSe), specifically, in patients with large tumors.

Methods: Consecutive patients with stage I-III breast cancer treated with NAC from November 2013 to March 2019 were identified. BCS eligibility before and after NAC was prospectively determined. Patients deemed BCSi before NAC due to large tumor size were studied. Statistical analyses were conducted using Student's t-test, Wilcoxon rank sum test, Chi-square test, Fisher's test, and logistic regression.

Results: In this study, 600 of 1353 cancers were BCSi with large tumors; 69% were non-BCS candidates, 31% were borderline-BCS (bBCS) candidates. Of non-BCS candidates, 69% became BCSe after NAC; 66% chose BCS, and 90% were successful. Among bBCS candidates, 87% were BCSe after NAC, 73% chose BCS, and 96% were successful. On univariate analysis, bBCS candidacy, lower cT stage, cN0 status, absence of calcifications, human epidermal growth factor receptor 2 positive (HER2+)/triple negative (TN) receptor status, poor differentiation, ductal histology, and breast pCR were associated with conversion to BCS eligibility. On multivariable analysis, receptor status (hormone receptor positive [HR+]/HER2- ref; odds ratio [OR] HER2+ 1.63, P = 0.047; HR-/HER2- OR, 2.26, P = 0.003) and breast pCR (OR 2.62, P < 0.001) predicted successful downstaging, while larger clinical tumor size (OR 0.86, P = 0.003), non-BCS candidacy (OR 0.46, P = 0.003), cN+ status (OR 0.54, P = 0.008), and calcifications (OR 0.56, P = 0.007) predicted lower downstaging rates.

Conclusion: In patients with large tumors precluding BCS, conversion to BCS eligibility was high with NAC, particularly in bBCS candidates. HER2+/TN receptor status predicted successful downstaging, while lower downstaging rates were observed with larger tumors, cN+ status, and calcifications. These factors should be considered when selecting patients for NAC.
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http://dx.doi.org/10.1245/s10434-020-08593-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722183PMC
January 2021

Georgia's collaborative approach to expanding mosquito surveillance in response to Zika virus: a case study.

US Army Med Dep J 2017 Jan-Jun(1-17):23-33

Department of Epidemiology and Environmental Health Science, Jiann-Ping Hsu College of Public Health, Georgia Southern University, Statesboro, Georgia.

Zika virus (ZIKV) was declared an international public health emergency by the World Health Organization on February 1, 2016. Due to the known and estimated range of the ZIKV mosquito vectors, southern and central US states faced increased risk of ZIKV transmission. With the state of Georgia hosting the world's busiest international airport, a climate that supports the ZIKV vectors, and limited surveillance (13 counties) and response capacity, the Department of Public Health (DPH) was challenged to respond and prevent ZIKV transmission. This case study describes and evaluates the state's surveillance capacity before and after the declaration of ZIKV as a public health emergency.

Method: We analyzed surveillance data from the DPH to compare the geographical distribution of counties conducting surveillance, total number, and overall percentage of mosquito species trapped in 2015 to 2016. Counties conducting surveillance before and after the identification of the ZIKV risk were mapped using ArcMap 10.4.1. Using SAS (version 9.2) (SAS Institute, Inc, Cary, NC), we performed the independent 2 sample t test to test for differences in prevalence in both years, and a χ² analysis to test for differences between numbers of species across the 13 counties. In addition, weighted frequency counts of mosquitoes were used to test (χ²) an association between major mosquito vector species and 7 urban counties. Lastly, using data from 2012-2016, a time-trend analysis was conducted to evaluate temporal trends in species prevalence.

Results: From 2015 to 2016, surveillance increased from 13 to 57 (338% increase) counties geographically dispersed across Georgia. A total of 76,052 mosquitoes were trapped and identified in 2015 compared to 144,731 (90.3% increase) in 2016. Significant differences between species (P<.001) and significant associations (P<.0001) between 7 urban counties and major mosquito vectors were found. Significant differences in prevalence were found between several species and year highlighting species-year temporal trends.

Conclusions: The DPH collaborative response to ZIKV allowed a rapid increase in its surveillance footprint. Existing and new partnerships were developed with the military and local health departments to expand and share data. This additional surveillance data allowed DPH to make sound public health decisions regarding mosquito-borne disease risks and close gaps in data related to vector distribution.
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February 2018

Utilization of smoking cessation medication benefits among medicaid fee-for-service enrollees 1999-2008.

PLoS One 2017 16;12(2):e0170381. Epub 2017 Feb 16.

Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.

Objective: To assess state coverage and utilization of Medicaid smoking cessation medication benefits among fee-for-service enrollees who smoked cigarettes.

Methods: We used the linked National Health Interview Survey (survey years 1995, 1997-2005) and the Medicaid Analytic eXtract files (1999-2008) to assess utilization of smoking cessation medication benefits among 5,982 cigarette smokers aged 18-64 years enrolled in Medicaid fee-for-service whose state Medicaid insurance covered at least one cessation medication. We excluded visits during pregnancy, and those covered by managed care or under dual enrollment (Medicaid and Medicare). Multivariate logistic regression was used to determine correlates of cessation medication benefit utilization among Medicaid fee-for-service enrollees, including measures of drug coverage (comprehensive cessation medication coverage, number of medications in state benefit, varenicline coverage), individual-level demographics at NHIS interview, age at Medicaid enrollment, and state-level cigarette excise taxes, statewide smoke-free laws, and per-capita tobacco control funding.

Results: In 1999, the percent of smokers with ≥1 medication claims was 5.7% in the 30 states that covered at least one Food and Drug Administration (FDA)-approved cessation medication; this increased to 9.9% in 2008 in the 44 states that covered at least one FDA-approved medication (p<0.01). Cessation medication utilization was greater among older individuals (≥ 25 years), females, non-Hispanic whites, and those with higher educational attainment. Comprehensive coverage, the number of smoking cessation medications covered and varenicline coverage were all positively associated with utilization; cigarette excise tax and per-capita tobacco control funding were also positively associated with utilization.

Conclusions: Utilization of medication benefits among fee-for-service Medicaid enrollees increased from 1999-2008 and varied by individual and state-level characteristics. Given that the Affordable Care Act bars state Medicaid programs from excluding any FDA-approved cessation medications from coverage as of January 2014, monitoring Medicaid cessation medication claims may be beneficial for informing efforts to increase utilization and maximize smoking cessation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0170381PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5313220PMC
August 2017

Gender-based differences in water, sanitation and hygiene-related diarrheal disease and helminthic infections: a systematic review and meta-analysis.

Trans R Soc Trop Med Hyg 2016 Nov;110(11):637-648

Department of Epidemiology and Environmental Health Sciences, Jiann-Ping Hsu College of Public Health, Georgia Southern University, GA, USA.

Background: Qualitative evidence suggests that inadequate water, sanitation and hygiene (WASH) may affect diarrheal and helminthic infection in women disproportionately. We systematically searched PubMed in June 2014 (updated 2016) and the WHO website, for relevant articles.

Methods: Articles dealing with the public health relevance of helminthic and diarrheal diseases, and highlighting the role of gender in WASH were included. Where possible, we carried out a meta-analysis.

Results: In studies of individuals 5 years or older, cholera showed lower prevalence in males (OR 0.56; 95% CI 0.34-0.94), while Schistosoma mansoni (1.38; 95% CI 1.14-1.67), Schistosoma japonicum (1.52; 95% CI 1.13-2.05), hookworm (1.43; 95% CI 1.07-1.89) and all forms of infectious diarrhea (1.21; 95% CI 1.06-1.38) showed a higher prevalence in males. When studies included all participants, S. mansoni and S. japonicum showed higher prevalence with males (OR 1.40; 95% CI 1.27-1.55 and 1.84; 95% CI 1.27-2.67, respectively). Prevalence of Trichiuris and hookworm infection showed effect modification with continent.

Conclusions: Evidence of gender differences in infection may reflect differences in gender norms, suggesting that policy changes at the regional level may help ameliorate gender related disparities in helminthic and diarrheal disease prevalence.
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http://dx.doi.org/10.1093/trstmh/trw080DOI Listing
November 2016

Gender disparities in water, sanitation, and global health.

Lancet 2015 Aug;386(9994):650-1

Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, Iowa City, IA, USA. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(15)61497-0DOI Listing
August 2015

Differential trends in cigarette smoking in the USA: is menthol slowing progress?

Tob Control 2015 Jan 30;24(1):28-37. Epub 2013 Aug 30.

The Schroeder Institute for Tobacco Research and Policy Studies at Legacy, Washington, District of Columbia, USA Department of Health, Behavior and Society, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA Department of Oncology, Georgetown University Medical Center, Lombardi Comprehensive Cancer Center, Washington, District of Columbia, USA.

Introduction: Mentholated cigarettes are at least as dangerous to an individual's health as non-mentholated varieties. The addition of menthol to cigarettes reduces perceived harshness of smoke, which can facilitate initiation. Here, we examine correlates of menthol use, national trends in smoking menthol and non-menthol cigarettes, and brand preferences over time.

Methods: We estimated menthol cigarette use during 2004-2010 using annual data on persons ≥12 years old from the National Surveys on Drug Use and Health. We adjusted self-reported menthol status for selected brands that were either exclusively menthol or non-menthol, based on sales data. Data were weighted to provide national estimates.

Results: Among cigarette smokers, menthol cigarette use was more common among 12-17 year olds (56.7%) and 18-25 year olds (45.0%) than among older persons (range 30.5% to 34.7%). In a multivariable analysis, menthol use was associated with being younger, female and of non-Caucasian race/ethnicity. Among all adolescents, the percentage who smoked non-menthol cigarettes decreased from 2004-2010, while menthol smoking rates remained constant; among all young adults, the percentage who smoked non-menthol cigarettes also declined, while menthol smoking rates increased. The use of Camel menthol and Marlboro menthol increased among adolescent and young adult smokers, particularly non-Hispanic Caucasians, during the study period.

Conclusions: Young people are heavy consumers of mentholated cigarettes. Progress in reducing youth smoking has likely been attenuated by the sale and marketing of mentholated cigarettes, including emerging varieties of established youth brands. This study should inform the Food and Drug Administration regarding the potential public health impact of a menthol ban.
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http://dx.doi.org/10.1136/tobaccocontrol-2013-051159DOI Listing
January 2015