Publications by authors named "Monica Morrow"

449 Publications

Local Recurrence is Frequent After Heroic Mastectomy for Classically Inoperable Breast Cancers.

Ann Surg Oncol 2021 Sep 14. Epub 2021 Sep 14.

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

Background: Despite advances in neoadjuvant systemic therapy (NST), some patients with aggressive T4 breast cancers do not respond. The efficacy of 'heroic' mastectomy in maintaining local control is unclear.

Methods: In consecutive patients with primary or recurrent T4 cancers with < 50% shrinkage on NST who underwent mastectomy from 2007 to 2017, clinicopathologic characteristics and locoregional recurrence (LRR) were examined.

Results: Among 104 patients, 59 (57%) had primary T4M0, 12 (12%) had locally recurrent T4M0, and 33 (32%) had T4M1 disease. Median age was 58.5 years and the majority had high-grade (74%) ductal cancers (85%); 45 (44%) were estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-), 26 (25%) were HER2 positive (HER2+), and 31 (30%) were triple negative (TN). Postoperative complications developed in 41 (39%) patients. At a median follow-up of 37 months, 42 (40%) patients developed LRR. TN (hazard ratio [HR] 7.5) and HER2+ (HR 2.67) subtypes, lymphovascular invasion (LVI; HR 3.80), and positive margins (HR 4.09) were predictive of LRR. The 3-year LRR rate was highest and overall survival (OS) was lowest among patients with TN cancers, at 66% (95% confidence interval [CI] 48-83%) and 30% (95% CI 14-47%), respectively.

Conclusions: After heroic mastectomy, postoperative complications were frequent and LRR occurred in 40% of patients despite a median OS of 3.8 years. Among TN patients, the 3-year LRR rate of 66% and 3-year OS of 30% suggest limited surgery benefit. Careful patient selection is prudent when considering heroic mastectomy.
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http://dx.doi.org/10.1245/s10434-021-10764-xDOI Listing
September 2021

Quality of Life and Breast Cancer Surgery.

Authors:
Monica Morrow

JAMA Surg 2021 Sep 1:e213759. Epub 2021 Sep 1.

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

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http://dx.doi.org/10.1001/jamasurg.2021.3759DOI Listing
September 2021

Association of Genetic Testing Results with Mortality Among Women with Breast Cancer or Ovarian Cancer.

J Natl Cancer Inst 2021 Aug 9. Epub 2021 Aug 9.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.

Background: Breast cancer and ovarian cancer patients increasingly undergo germline genetic testing. However, little is known about cancer-specific mortality among carriers of a pathogenic variant (PV) in BRCA1/2 or other genes in a population-based setting.

Methods: Georgia and California Surveillance Epidemiology and End Results (SEER) registry records were linked to clinical genetic testing results. Women were included who had stages I-IV breast cancer or ovarian cancer diagnosed in 2013-2017; received chemotherapy; and linked to genetic testing results. Multivariable Cox proportional hazard models were used to examine the association of genetic results with cancer-specific mortality.

Results: 22,495 breast and 4,320 ovarian cancer patients were analyzed, with a median follow-up of 41 months. PVs were present in 12.7% of breast cancer patients with estrogen and/or progesterone receptor-positive, HER2-negative cancer, 9.8% with HER2-positive cancer, 16.8% with triple-negative breast cancer and 17.2% with ovarian cancer. Among triple-negative breast cancer patients, cancer-specific mortality was lower with BRCA1 (hazard ratio [HR] = 0.49, 95% confidence interval [CI] = 0.35-0.69) and BRCA2 PVs (HR = 0.60, 95% CI = 0.41-0.89), and equivalent with PVs in other genes (HR = 0.65, 95% CI = 0.37-1.13), versus non-carriers. Among ovarian cancer patients, cancer-specific mortality was lower with PVs in BRCA2 (HR = 0.35, 95% CI = 0.25-0.49) and genes other than BRCA1/2 (HR = 0.47, 95% CI = 0.32-0.69). No PV was associated with higher cancer-specific mortality.

Conclusions: Among breast cancer and ovarian cancer patients treated with chemotherapy in the community, BRCA1/2 and other gene PV carriers had equivalent or lower short-term cancer-specific mortality than non-carriers. These results may reassure newly diagnosed patients and longer follow-up is ongoing.
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http://dx.doi.org/10.1093/jnci/djab151DOI Listing
August 2021

ASO Visual Abstract: Margin Width and Local Recurrence in Patients Undergoing Breast Conservation after Neoadjuvant Chemotherapy.

Ann Surg Oncol 2021 Aug 7. Epub 2021 Aug 7.

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

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http://dx.doi.org/10.1245/s10434-021-10574-1DOI Listing
August 2021

Margin Width and Local Recurrence in Patients Undergoing Breast Conservation After Neoadjuvant Chemotherapy.

Ann Surg Oncol 2021 Jul 30. Epub 2021 Jul 30.

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

Background: A margin of "no ink on tumor" has been established for primary breast conservation therapy (BCT), but the appropriate margin following neoadjuvant chemotherapy (NAC) remains controversial. We examined the impact of margin width on ipsilateral breast tumor recurrence (IBTR) in the NAC-BCT population.

Methods: Consecutive patients receiving NAC-BCT were identified from a prospective database. The associations between clinicopathologic characteristics, margin width, and isolated IBTR were evaluated.

Results: From 2013 to 2019 we identified 582 patients with 586 tumors who received NAC-BCT. The median age of the cohort was 54 years (IQR 45, 62); 84% of patients had cT1/T2 tumors and 61% were clinically node positive. The majority of tumors were HER2+ (38%) or triple negative (TN) (31%). Pathologic complete response was observed in 29%. Margin width was > 2 mm in 517 tumors (88%) and ≤ 2 mm in 69 (12%). At a median follow-up of 39 months, 14 patients had IBTR as a first event, with 64% occurring within 24 months of surgery. The 4-year IBTR rate was 2% (95% CI 1-4%), and there was no difference based on margin width (3% ≤ 2 mm vs 2% > 2 mm; p = not significant). On univariate analysis, clinical and pathologic T stage and receptor subtype, but not margin width, were associated with IBTR (p < 0.05). On multivariable analysis, TN subtype and higher pathologic T stage were associated with isolated IBTR (both p < 0.05).

Conclusion: Pathologic features and tumor biology, not margin width, were associated with IBTR in NAC-BCT patients.
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http://dx.doi.org/10.1245/s10434-021-10533-wDOI Listing
July 2021

Blood Biomarkers Reflect the Effects of Obesity and Inflammation on the Human Breast Transcriptome.

Carcinogenesis 2021 Jul 27. Epub 2021 Jul 27.

Retired, Department of Medicine, Weill Cornell Medical College, New York, New York.

Obesity is a risk factor for the development of post-menopausal breast cancer. Breast white adipose tissue (WAT) inflammation, which is commonly found in women with excess body fat, is also associated with increased breast cancer risk. Both local and systemic effects are likely to be important for explaining the link between excess body fat, adipose inflammation and breast cancer. The first goal of this cross-sectional study of 196 women was to carry out transcriptome profiling to define the molecular changes that occur in the breast related to excess body fat and WAT inflammation. A second objective was to determine if commonly measured blood biomarkers of risk and prognosis reflect molecular changes in the breast. Breast WAT inflammation was assessed by immunohistochemistry. Bulk RNA-sequencing was carried out to assess gene expression in non-tumorous breast. Obesity and WAT inflammation were associated with a large number of differentially expressed genes and changes in multiple pathways linked to the development and progression of breast cancer. Altered pathways included inflammatory response, complement, KRAS signaling, TNFα signaling via NFкB, IL6-JAK-STAT3 signaling, epithelial mesenchymal transition, angiogenesis, interferon γ response, and TGF-β signaling. Increased expression of several drug targets such as aromatase, TGF-β1, IDO-1 and PD-1 were observed. Levels of various blood biomarkers including hsCRP, IL6, leptin, adiponectin, triglycerides, HDL cholesterol and insulin were altered and correlated with molecular changes in the breast. Collectively, this study helps to explain both the link between obesity and breast cancer and the utility of blood biomarkers for determining risk and prognosis.
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http://dx.doi.org/10.1093/carcin/bgab066DOI Listing
July 2021

Poor response to neoadjuvant chemotherapy in metaplastic breast carcinoma.

NPJ Breast Cancer 2021 Jul 22;7(1):96. Epub 2021 Jul 22.

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

Metaplastic breast carcinoma (MpBC) is a rare special histologic subtype of breast carcinoma characterized by the presence of squamous and/or mesenchymal differentiation. Most MpBCs are of triple-negative phenotype and neoadjuvant chemotherapy (NAC) is frequently utilized in patients with MpBC. The aim of this study was to evaluate response to NAC in a retrospective cohort of MpBCs. We identified 44 patients with MpBC treated with NAC at our center between 2002 and 2018. Median age was 48 years, 86% were clinical stage II-III, and 36% were clinically node-positive. Most (80%) MpBCs were triple-negative or low (1-10%) hormonal receptor positive and HER2 negative on pre-NAC biopsy. While on NAC, 49% showed no clinical response or clinico-radiological progression. Matrix-producing subtype was associated with clinico-radiological response (p = 0.0036). Post NAC, two patients initially ineligible for breast-conserving surgery (BCS) were downstaged to be eligible for BCS, whereas three patients potentially eligible for BCS before treatment became ineligible due to disease progression. Only one (2%) patient had a pathologic complete response (pCR). Among the 16 patients presenting with biopsy-proven clinical node-positive disease, 3 (19%) had nodal pCR. Axillary lymph node dissection was avoided in 3 (19%) patients who had successful axillary downstaging. Residual cancer burden (RCB) was assessed in 22 patients and was significantly associated with disease-free survival and overall survival. We observed a poor response or even disease progression on NAC among patients with MpBC, suggesting that NAC should be reserved for patients with inoperable MpBC.
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http://dx.doi.org/10.1038/s41523-021-00302-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298632PMC
July 2021

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

Breast Cancer Res Treat 2021 Sep 14;189(2):307-315. 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
September 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 Oct 10;28(10):5507-5512. 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
October 2021

Breast-conserving Surgery Without Radiation Therapy for Invasive Cancer.

Clin Breast Cancer 2021 04 6;21(2):112-119. Epub 2021 Jan 6.

Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address:

Radiotherapy (RT) after breast-conserving surgery (BCS) halves the risk of local recurrence, and it is considered the standard of care for the vast majority of patients with early invasive breast cancer. However, the majority of patients treated with BCS will not recur locally, even in the absence of RT. Over the past several decades, the improved and widespread use of systemic therapy has significantly decreased the rate of local recurrence. This has stimulated interest in identifying favorable patient subsets not requiring RT. Randomized controlled trials have shown in women aged ≥ 70 years with stage I estrogen receptor-positive (ER) tumors, RT can be safely omitted. To better identify patients with favorable prognosis, ongoing trials have incorporated biological markers and genomic assays. Despite great research efforts to de-escalate locoregional treatment, real-world data indicate that omission of RT in low-risk patients is inconsistent. Better decision-making is warranted to reduce overtreatment and financial toxicity.
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http://dx.doi.org/10.1016/j.clbc.2021.01.001DOI Listing
April 2021

Reply to: "Ketorolac Following Mastectomy: Is There an Increased Risk of Reoperation?"

Ann Surg Oncol 2021 May 7. Epub 2021 May 7.

Departments of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

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http://dx.doi.org/10.1245/s10434-021-10073-3DOI Listing
May 2021

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

J Am Coll Surg 2021 Aug 3;233(2):285-293. 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
August 2021

Is Residual Nodal Disease at Axillary Dissection Associated with Tumor Subtype in Patients with Low Volume Sentinel Node Metastasis After Neoadjuvant Chemotherapy?

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: In patients with a positive sentinel lymph node (SLN) after neoadjuvant chemotherapy (NAC), the likelihood of residual nodal disease at axillary dissection (ALND) is high. Whether non-SLN metastasis frequency varies based on tumor subtype and SLN metastasis size is uncertain. We examined the association between tumor subtype and frequency of non-SLN metastases in patients with SLN micro- vs macrometastases after NAC.

Methods: Patients with invasive breast cancer and a positive SLN biopsy after NAC between July 2008 and July 2019 were identified. Associations between tumor subtype, SLN disease volume, and frequency of non-SLN metastases were examined.

Results: Among 273 patients with ≥ 1 positive SLN and a completion ALND, mean age was 51 years, 87% of tumors were ductal, 80% were clinically node-positive at presentation, and 85% were cT2-3. The frequency of non-SLN metastases was non-significantly higher in HR+/HER2- (61%) vs. HER2+ (52%) and triple negative tumors (45%) (p = 0.09). Frequency of SLN micrometastasis was 9% for triple negative tumors compared with 17% for HR+/HER2- and 34% for HER2+ tumors (p = 0.015). Size of SLN metastasis (micro- vs. macrometastases) was not associated with non-SLN metastasis frequency or number within any subtype.

Conclusions: In patients with a positive SLN after NAC, the likelihood of non-SLN metastasis at ALND was high across all tumor subtypes and did not vary significantly for SLN micro- versus macrometastases. ALND is recommended for SLN micro- and macrometastases after NAC, irrespective of tumor subtype.
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http://dx.doi.org/10.1245/s10434-021-09910-2DOI Listing
April 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

ASO Author Reflections: Rethinking Palpable Adenopathy as a Marker of 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.

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http://dx.doi.org/10.1245/s10434-021-09984-yDOI 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

Morphologic subtypes of lobular carcinoma in situ diagnosed on core needle biopsy: clinicopathologic features and findings at follow-up excision.

Mod Pathol 2021 08 6;34(8):1495-1506. Epub 2021 Apr 6.

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

Lobular carcinoma in situ (LCIS) is currently classified as classic (CLCIS), florid (FLCIS), and pleomorphic (PLCIS). Given the rarity of FLCIS and PLCIS, information on their clinico-pathologic features and biologic potential remains limited. We evaluated the upgrade rates at excision of FLCIS and PLCIS diagnosed on inhouse core needle biopsy (CNB) and their clinical presentation and follow-up. Over a period of 11 and a half years, there were a total of 36 inhouse CNBs with pure PLCIS (n = 8), FLCIS (n = 24), or LCIS with pleomorphic features (LCIS-PF) (n = 4). The upgrade rates to invasive carcinoma or ductal carcinoma in situ (DCIS) were 25% for PLCIS (2/8), 17% for FLCIS (4/24), and 0% for LCIS-PF (0/4). The overall upgrade rate of PLCIS and FLCIS combined was 19% (6/32). All but one case (not upgraded at excision) were radiologic-pathologic concordant. Apocrine features, previously reported only in PLCIS, were also noted in FLCIS. HER2 overexpression was seen in 13% of cases. This study highlights the more aggressive biologic features of PLCIS and FLCIS compared to CLCIS and supports surgical management for these lesions.
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http://dx.doi.org/10.1038/s41379-021-00796-9DOI Listing
August 2021

Breast cancer.

Lancet 2021 May 1;397(10286):1750-1769. Epub 2021 Apr 1.

European Institute of Oncology IRCCS, Milan, Italy; University of Milano, Milan, Italy.

Breast cancer is still the most common cancer worldwide. But the way breast cancer is viewed has changed drastically since its molecular hallmarks were extensively characterised, now including immunohistochemical markers (eg, ER, PR, HER2 [ERBB2], and proliferation marker protein Ki-67 [MKI67]), genomic markers (eg, BRCA1, BRCA2, and PIK3CA), and immunomarkers (eg, tumour-infiltrating lymphocytes and PD-L1). New biomarker combinations are the basis for increasingly complex diagnostic algorithms. Neoadjuvant combination therapy, often including targeted agents, is a standard of care (especially in HER2-positive and triple-negative breast cancer), and the basis for de-escalation of surgery in the breast and axilla and for risk-adapted post-neoadjuvant strategies. Radiotherapy remains an important cornerstone of breast cancer therapy, but de-escalation schemes have become the standard of care. ER-positive tumours are treated with 5-10 years of endocrine therapy and chemotherapy, based on an individual risk assessment. For metastatic breast cancer, standard therapy options include targeted approaches such as CDK4 and CDK6 inhibitors, PI3K inhibitors, PARP inhibitors, and anti-PD-L1 immunotherapy, depending on tumour type and molecular profile. This range of treatment options reflects the complexity of breast cancer therapy today.
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http://dx.doi.org/10.1016/S0140-6736(20)32381-3DOI Listing
May 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

Effects of obesity on breast aromatase expression and systemic metabo-inflammation in women with BRCA1 or BRCA2 mutations.

NPJ Breast Cancer 2021 Mar 1;7(1):18. Epub 2021 Mar 1.

Departments of Medicine, Weill Cornell Medical College, New York, NY, USA.

Obesity is associated with an increased risk of breast cancer in post-menopausal women and decreased risk in pre-menopausal women. Conversely, in BRCA1/2 mutation carriers, pre-menopausal obesity is associated with early-onset breast cancer. Here we show that obese, pre-menopausal BRCA1/2 mutation carriers have increased levels of aromatase and inflammation in the breast, as occurs in post-menopausal women. In a prospective cohort study of 141 women with germline BRCA1 (n = 74) or BRCA2 (n = 67) mutations, leptin, and aromatase expression were higher in the breast tissue of obese versus lean individuals (P < 0.05). Obesity was associated with breast white adipose tissue inflammation, which correlated with breast aromatase levels (P < 0.01). Circulating C-reactive protein, interleukin-6, and leptin positively correlated with body mass index and breast aromatase levels, whereas negative correlations were observed for adiponectin and sex hormone-binding globulin (P < 0.05). These findings could help explain the increased risk of early-onset breast cancer in obese BRCA1/2 mutation carriers.
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http://dx.doi.org/10.1038/s41523-021-00226-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921427PMC
March 2021

Effects of Adiposity and Exercise on Breast Tissue and Systemic Metabo-Inflammatory Factors in Women at High Risk or Diagnosed with Breast Cancer.

Cancer Prev Res (Phila) 2021 May 1;14(5):541-550. Epub 2021 Mar 1.

Department of Medicine, Weill Cornell Medical College, New York, New York.

Excess body fat and sedentary behavior are associated with increased breast cancer risk and mortality, including in normal weight women. To investigate underlying mechanisms, we examined whether adiposity and exercise impact the breast microenvironment (e.g., inflammation and aromatase expression) and circulating metabo-inflammatory factors. In a cross-sectional cohort study, breast white adipose tissue (WAT) and blood were collected from 100 women undergoing mastectomy for breast cancer risk reduction or treatment. Self-reported exercise behavior, body composition measured by dual-energy x-ray absorptiometry (DXA), and waist:hip ratio were obtained prior to surgery. Breast WAT inflammation (B-WATi) was assessed by IHC and aromatase expression was assessed by quantitative PCR. Metabolic and inflammatory blood biomarkers that are predictive of breast cancer risk and progression were measured. B-WATi was present in 56 of 100 patients and was associated with older age, elevated BMI, postmenopausal status, decreased exercise, hypertension and dyslipidemia (s < 0.001). Total body fat and trunk fat correlated with B-WATi and breast aromatase levels (s < 0.001). Circulating C-reactive protein, IL6, insulin, and leptin positively correlated with body fat and breast aromatase levels, while negative correlations were observed for adiponectin and sex hormone binding globulin ( < 0.001). Inverse relationships were observed with exercise (s < 0.05). In a subgroup of 39 women with normal BMI, body fat levels positively correlated with B-WATi and aromatase expression (s < 0.05). In conclusion, elevated body fat levels and decreased exercise are associated with protumorigenic micro- and host environments in normal, overweight, and obese individuals. These findings support the development of BMI-agnostic lifestyle interventions that target adiposity. PREVENTION RELEVANCE: We report that individuals with high body fat and low exercise levels have breast inflammation, higher breast aromatase expression, and levels of circulating metabo-inflammatory factors that have been associated with increased breast cancer risk. These findings support interventions to lower adiposity, even among normal weight individuals, to prevent tumor growth.
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http://dx.doi.org/10.1158/1940-6207.CAPR-20-0507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102399PMC
May 2021

Intraoperative Ketorolac is Associated with Risk of Reoperation After Mastectomy: A Single-Center Examination.

Ann Surg Oncol 2021 Sep 24;28(9):5134-5140. Epub 2021 Feb 24.

Department of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: Although ketorolac is an effective adjunct for managing pain in the perioperative period, it is associated with a risk of postoperative bleeding. This study retrospectively investigated the association between ketorolac use and both reoperation and postoperative opioid use among mastectomy patients.

Methods: The study identified all women undergoing mastectomy (unilaterally or bilaterally) at our ambulatory surgery cancer center from January 2016 to June 2019. The primary outcome was reoperation for bleeding on postoperative day 0 or 1, and the secondary outcome was postoperative opioid use. The association between ketorolac and outcomes was assessed using multivariable regression models. The covariates were age, body mass index, breast reconstruction, bilateral surgery, peripheral nerve block, and preoperative antiplatelet and/or anticoagulation medication.

Results: A cohort of 3469 women were identified. Ketorolac was given to 1549 (45%) of the women, with 922 women (60%) receiving 30 mg and 627 women (40%) receiving 15 mg. The overall reoperation rate for bleeding was 3.1% (1.8% without ketorolac vs 4.8% with ketorolac). In the multivariable analysis, ketorolac was associated with a higher risk of reoperation [odds ratio (OR) 2.43; 95% confidence interval (CI) 1.60-3.70; P < 0.0001]. Ketorolac also was associated with a lower proportion of patients receiving any postoperative narcotic within 24 h (15 mg: OR 0.73; 95% CI 0.57-0.94; P = 0.014 vs 30 mg: OR 0.52; 95% CI 0.42-0.66; P < 0.0001).

Conclusions: Ketorolac use decreased postoperative opioid use, but this benefit was outweighed by the increased risk of bleeding requiring reoperation. This finding led to a change in practice at the authors' center, with ketorolac no longer administered in the perioperative care of the mastectomy patient.
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http://dx.doi.org/10.1245/s10434-021-09722-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355042PMC
September 2021

Time Trends in Receipt of Germline Genetic Testing and Results for Women Diagnosed With Breast Cancer or Ovarian Cancer, 2012-2019.

J Clin Oncol 2021 May 9;39(15):1631-1640. Epub 2021 Feb 9.

Department of Health Management and Policy, School of Public Health, Department of Biostatistics, University of Michigan, Ann Arbor, MI.

Purpose: Genetic testing is important for breast and ovarian cancer risk reduction and treatment, yet little is known about its evolving use.

Methods: SEER records of women of age ≥ 20 years diagnosed with breast or ovarian cancer from 2013 to 2017 in California or Georgia were linked to the results of clinical germline testing through 2019. We measured testing trends, rates of variants of uncertain significance (VUS), and pathogenic variants (PVs).

Results: One quarter (25.2%) of 187,535 patients with breast cancer and one third (34.3%) of 14,689 patients with ovarian cancer were tested; annually, testing increased by 2%, whereas the number of genes tested increased by 28%. The prevalence of test results by gene category for breast cancer cases in 2017 were PVs 5.2%, and VUS 0.8%; breast cancer-associated genes or ovarian cancer-associated genes ( and ), PVs 3.7%, and VUS 12.0%; other actionable genes ( and ) PVs 0.6%, and VUS 0.5%; and other genes, PVs 0.3%, and VUS 2.6%. For ovarian cancer cases in 2017, the prevalence of test results were , PVs 11.0%, and VUS 0.9%; breast or ovarian genes, PVs 4.0%, and VUS 12.6%; other actionable genes, PVs 0.7%, and VUS 0.4%; and other genes, PVs 0.3%, and VUS 0.6%. VUS rates doubled over time (2013 diagnoses: 11.2%; 2017 diagnoses: 26.8%), particularly for racial or ethnic minorities (47.8% Asian and 46.0% Black, 24.6% non-Hispanic White patients; < .001).

Conclusion: A testing gap persists for patients with ovarian cancer (34.3% tested nearly all recommended), whereas adding more genes widened a racial or ethnic gap in VUS results. Most PVs were in 20 breast cancer-associated genes or ovarian cancer-associated genes; testing other genes yielded mostly VUS. Quality improvement should focus on testing indicated patients rather than adding more genes.
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http://dx.doi.org/10.1200/JCO.20.02785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274804PMC
May 2021

Individualizing Surveillance Mammography for Older Patients After Treatment for Early-Stage Breast Cancer: Multidisciplinary Expert Panel and International Society of Geriatric Oncology Consensus Statement.

JAMA Oncol 2021 Apr;7(4):609-615

Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts.

Importance: There is currently no guidance on how to approach surveillance mammography for older breast cancer survivors, particularly when life expectancy is limited.

Objective: To develop expert consensus guidelines that facilitate tailored decision-making for routine surveillance mammography for breast cancer survivors 75 years or older.

Evidence: After a literature review of the risk of ipsilateral and contralateral breast cancer events among breast cancer survivors and the harms and benefits associated with mammography, a multidisciplinary expert panel was convened to develop consensus guidelines on surveillance mammography for breast cancer survivors 75 years or older. Using an iterative consensus-based approach, input from clinician focus groups, and critical review by the International Society for Geriatric Oncology, the guidelines were refined and finalized.

Findings: The literature review established a low risk for ipsilateral and contralateral breast cancer events in most older breast cancer survivors and summarized the benefits and harms associated with mammography. Draft mammography guidelines were iteratively evaluated by the expert panel and clinician focus groups, emphasizing a patient's risk for in-breast cancer events, age, life expectancy, and personal preferences. The final consensus guidelines recommend discontinuation of routine mammography for all breast cancer survivors when life expectancy is less than 5 years, including those with a history of high-risk cancers; consideration to discontinue mammography when life expectancy is 5 to 10 years; and continuation of mammography when life expectancy is more than 10 years. Individualized, shared decision-making is encouraged to optimally tailor recommendations after weighing the benefits and harms associated with surveillance mammography and patient preferences. The panel also recommends ongoing clinical breast examinations and diagnostic mammography to evaluate clinical findings and symptoms, with reassurance for patients that these practices will continue.

Conclusions And Relevance: It is anticipated that these expert guidelines will enhance clinical practice by providing a framework for individualized discussions, facilitating shared decision-making regarding surveillance mammography for breast cancer survivors 75 years or older.
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http://dx.doi.org/10.1001/jamaoncol.2020.7582DOI Listing
April 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

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

Concordance Between 21-Gene Recurrence Scores in Multifocal or Multicentric Breast Carcinomas Differs by Age and Histologic Subtype.

Ann Surg Oncol 2021 Aug 3;28(8):4256-4262. Epub 2021 Jan 3.

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

Background: Among patients with multifocal or multicentric (MF/MC) breast cancer (BC) of similar morphology, concordance in Oncotype DX recurrence scores (RS) between tumors has been reported to be 87%. The effect of age and variation in histologic subtypes on RS concordance according to TAILORx criteria is unknown.

Methods: We identified patients with MF/MC, estrogen receptor-positive, HER2-negative, node-negative BC with two or more RS results treated at our institution from 2009 to 2018. Patients were analyzed by age group (≤ 50 and > 50 years). Low- and high-risk cut-offs were RS ≤ 25 and > 25 for age > 50 years, and RS ≤ 20 and > 20 for age ≤ 50 years. RS concordance was defined as no change in management based on RS variation between lesions.

Results: Overall, 120 patients with MF/MC BC were identified-82 (68.3%) aged > 50 years and 38 (31.7%) aged ≤ 50 years. Patients aged ≤ 50 years had higher mean RS for both multifocal (20 vs. 14; p = 0.006) and multicentric (17 vs. 13; p = 0.003) tumors and more frequently had high-risk tumors (p < 0.0001). Among patients aged > 50 years, 95.1% had RS concordance between tumors (same subtype, 98.2%; variable subtype, 88.9%; p = 0.1). Among patients aged ≤ 50 years, RS concordance was 81.6%.

Conclusions: Among patients with MF/MC BC, RS concordance was high, particularly in those aged > 50 years with tumors of the same histologic subtype. RS testing of one focus may be sufficiently prognostic and predictive in patients aged > 50 years, regardless of subtype concordance. Testing of individual foci should be considered in patients aged ≤ 50 years due to a higher likelihood of RS discordance.
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http://dx.doi.org/10.1245/s10434-020-09429-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253864PMC
August 2021
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