Faculty Bibliography

Purpose/Objective(s): Breast re-irradiation (reRT) after repeat breast conserving surgery (BCS) has emerged as a viable alternative to mastectomy in women presenting with low risk in-breast tumor recurrence (IBTR). However, there is limited data on optimal patient selection and safety of different fractionation regimens. This multi-institutional study reports safety and efficacy in a large cohort of women with IBTR treated with repeat BCS and reRT. Materials/Methods: Using electronic medical record search tools, we identified all patients who underwent repeat BCS followed by breast reRT from 2015-2021 at 2 institutions. Univariate logistic regression models were used to identify clinical and dosimetric factors associated with development of acute and late toxicities. All statistical tests were two-sided, and the null hypothesis was rejected for p<0.05. Kaplan Meier methodology was used to calculate overall survival (OS), disease-free survival (DFS) and locoregional recurrence-free survival (LR-RFS).
Result(s): We identified 66 patients with an IBTR treated with repeat BCS. In the initial RT course, 55% received whole breast RT (WBI) with conventional fractionation (<=2 Gy/fraction[fx]), 29% WBI with hypofractionation (2.6-2.7 Gy/fx), 6% partial breast irradiation (PBI) ultrahypofractionation (6-8 Gy/fx) and 11% had unavailable treatment details. There was a median of 11 years between initial breast cancer and IBTR. At time of recurrence, 36% of patients had tumors located in the same quadrant as the initial cancer, 41% had invasive carcinoma with ductal carcinoma in situ (DCIS), 41% had invasive carcinoma alone, 18% had DCIS alone, 92% had tumors < 2 cm, 68% had low-intermediate grade tumors and all were clinically node negative. For reRT, 95% received PBI (57.5% 45 Gy/1.5 Gy twice daily; 27% 45 Gy/1.8 Gy daily; 10.5% hypofractionation), and 5% received WBI (45-46.8 Gy in 1.8 Gy/fx), all of whom had received PBI for the initial course. Nine patients (13%) underwent adjuvant chemotherapy and 44 (67%) adjuvant hormone therapy. Median follow-up was 16 months (range 3-60). Twenty-one patients (32%) experienced any acute >= grade 2 events, and 17 (26%) experienced any late >= grade 2 toxicities. One patient experienced grade 3 fibrosis and one patient experienced grade 3 telangiectasia at 36 months. None had grade 4 or higher late adverse events. We found no association between fractionation of reRT or cumulative dose (measured as EQD2) with acute or late toxicity. At 2 years, OS was 100%, DMFS was 91.6%, and LR-RFS was 100%.
Conclusion(s): In this large multi-institutional series of patients with recurrent breast cancer, second breast conservation surgery followed by reRT was effective with no local recurrences and excellent disease control outcomes, and toxicity appears to be acceptable. Longer follow-up and more prospective study are needed to further inform patient selection and establish the efficacy and tolerability of repeat breast conservation therapy in the setting of limited, low-risk recurrence.
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Superior vena cava (SVC) syndrome is commonly caused by malignancy but is rarely associated with breast cancer. The following case series describes three female breast cancer patients who were found to have disease recurrence years after initial diagnosis, presenting as facial swelling, collateral vessel formation, and shortness of breath consistent with SVC syndrome. All patients were treated with radiation therapy, and one patient required stenting due to tumor thrombus in the SVC. These cases highlight a rare complication of breast cancer that clinicians should recognize in patients who have undergone treatment particularly for right sided breast cancer with lymph node involvement.

PURPOSE:Provide real-world data regarding the risk for SARS-CoV-2 infection and mortality in breast cancer (BC) patients on active cancer treatment. METHODS:Clinical data were abstracted from the 3778 BC patients seen at a multisite cancer center in New York between February 1, 2020 and May 1, 2020, including patient demographics, tumor histology, cancer treatment, and SARS-CoV-2 testing results. Incidence of SARS-CoV-2 infection by treatment type (chemotherapy [CT] vs endocrine and/or HER2 directed therapy [E/H]) was compared by Inverse Probability of Treatment Weighting. In those diagnosed with SARS-CoV-2 infection, Mann-Whitney test was used to a assess risk factors for severe disease and mortality. RESULTS:Three thousand sixty-two patients met study inclusion criteria with 641 patients tested for SARS-COV-2 by RT-PCR or serology. Overall, 64 patients (2.1%) were diagnosed with SARS-CoV-2 infection by either serology, RT-PCR, or documented clinical diagnosis. Comparing matched patients who received chemotherapy (n = 379) with those who received non-cytotoxic therapies (n = 2343) the incidence of SARS-CoV-2 did not differ between treatment groups (weighted risk; 3.5% CT vs 2.7% E/H, P = .523). Twenty-seven patients (0.9%) expired over follow-up, with 10 deaths attributed to SARS-CoV-2 infection. Chemotherapy was not associated with increased risk for death following SARS-CoV-2 infection (weighted risk; 0.7% CT vs 0.1% E/H, P = .246). Advanced disease (stage IV), age, BMI, and Charlson's Comorbidity Index score were associated with increased mortality following SARS-CoV-2 infection (P ≤ .05). CONCLUSION:BC treatment, including chemotherapy, can be safely administered in the context of enhanced infectious precautions, and should not be withheld particularly when given for curative intent.

Background: PD-1/PD-L1 checkpoint blockade in combination with chemotherapy has improved outcomes in triple-negative breast cancer, but its role in hormone receptor-positive (HR+) metastatic breast cancer (MBC) is less clear. We report the results of the HR+ cohort of a HER2-negative MBC trial.
Method(s): Prospective phase 2 trial where 20 HR+/HER2- MBC patients (pts) received nab-paclitaxel (A) (100mg/m2 IV d1/8, q 3 wks) and pembrolizumab (P) (200mg IV d1, q 3 wks, starting with cycle 2). Eligibility: ER/PR >=1%, HER2 negative, maximum of 2 lines of cytotoxic therapy for MBC, pts could have received prior endocrine and/or targeted therapy. Primary endpoint: best overall response rate (BORR) by RECIST v1.1; secondary endpoints: safety, PFS, clinical benefit rate (CBR), duration of response (DOR), and overall survival (OS). Biomarker analyses are ongoing.
Result(s): In this 20-patient cohort, the median age was 56 (34-75), median lines of cytotoxic chemotherapy was 1 (0-2), 70% (14/20) were ER>10%, 80% (16/20) received prior hormone therapy, and 60% (12/20) received prior CDK 4/6 inhibitors. BORR was partial response (PR) in 5/20, stable disease (SD) in 7/20, and progressive disease (PD) in 7/20. CBR was 35% (7/20). Median PFS was 5.6 mos (95%CI 2.07-8.18), median OS 15.7 mos (95%CI 3.88-27.70) and median DOR was 3.9 mos (95%CI 2.07-not yet reached). Out of 5 pts who achieved PR, 4 (80%) received prior CDK 4/6 inhibitors. The most common related adverse events (AE) were anemia (50%), diarrhea, nausea and ALT abnormalities (40% each). 14 pts experienced grade 3 AEs, the most common being neutropenia, 1 pt had grade 4 AEs (pneumonitis, blood/lymphatics, hyponatremia), and no grade 5 AEs. [Formula presented]
Conclusion(s): P plus A was efficacious with PR in 5/20 and SD in 7/20 pts with a manageable toxicity profile. Importantly, responses were observed in patients previously treated with CDK 4/6 inhibitors. Further investigation of this regimen in HR+/HER2- MBC is warranted. Clinical trial identification: NCT02752685. Legal entity responsible for the study: NYU Langone Health.
Funding(s): Merck (drug-pembrolizumab and financial funding); Celgene (drug-nab-paclitaxel). Disclosure: F. Muggia: Advisory/Consultancy, Member of data safety monitoring committee of Pembrolizumab trials run by Merck: Merck. S. Adams: Advisory/Consultancy, Research grant/Funding (institution), consultant (uncompensated): Merck; Research grant/Funding (institution): Celgene. All other authors have declared no conflicts of interest.
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BACKGROUND:Women with breast cancer have worse health outcomes with co-occurring type 2 diabetes, possibly due to suboptimal breast cancer treatment. METHODS:We created a cohort of women ages 66 to 85 y with stage I to III breast cancer from 1993 to 2012 from an integrated health care delivery system (n=1612) and fee-for-service Medicare beneficiaries (n=98,915), linked to Surveillance, Epidemiology, and End Results (SEER) data (total n=100,527). We evaluated associations between type 2 diabetes and other factors with undergoing guideline-concordant cancer treatment. We estimated χ tests for univariate analysis and relative risks (RRs) using multivariable log-binomial models for outcomes of (1) overall guideline-concordant treatment, (2) definitive surgical therapy (mastectomy or lumpectomy with radiation), (3) chemotherapy if indicated, and (4) endocrine therapy. RESULTS:Our cohort included 60% of subjects with stage 1 tumors, one quarter below 70 years old, 23% had diabetes, 35% underwent overall guideline-concordant treatment, 24% chemotherapy, and 83% endocrine therapy. Women with diabetes were less likely to undergo overall guideline-concordant treatment (RR: 0.96; 95% confidence interval: 0.94-0.98), and only slightly less likely to undergo guideline-concordant definitive surgical therapy (RR: 0.99; 95% confidence interval: 0.99-1.00). No differences were found for chemotherapy or endocrine therapy. Other factors significantly associated with a lower risk of guideline-concordant care were cancer stages II to III (vs. I; RR=0.47-0.69, P<0.0001), older age (vs. 66 to 69 y; RR=0.56-0.90, P<0.0001), higher comorbidity burden, and Medicaid dual-eligibility. CONCLUSIONS:Diabetes was associated with lower adherence to overall guideline-concordant breast cancer treatment. However, higher stage, older age, higher comorbidity burden, and Medicaid insurance were more strongly associated with lower use of guideline-concordant treatment. Given the heavy burden of breast cancer and diabetes, long-term outcomes analysis should consider guideline-concordant treatment. IMPACT/CONCLUSIONS:Other factors besides diabetes are more strongly associated with guideline-concordant breast cancer treatment.

Many women diagnosed with breast cancer have chronic conditions such as diabetes that may impact other health behaviors. Our purpose was to determine if breast cancer screening and detection differs among women with and without diabetes. We conducted a cross-sectional analysis of a retrospective cohort of women aged 52-74 years diagnosed with incident stages I-III breast cancer enrolled in an integrated health plan between 1999 and 2014 with linkage to the Surveillance, Epidemiology and End Results registry (n = 2040). Screening data were taken from electronic health records. We used multivariable modified Poisson regression models with robust standard errors to estimate relative risks (RR) and 95% confidence intervals (CI) for outcomes of (i) receipt of screening in the 2 years prior to diagnosis; (ii) symptom-detected breast cancer; and (iii) diagnosis of locally advanced stage III breast cancer. Compared to women without diabetes, women with diabetes were similar with respect to receipt of screening mammography (78% and 77%), symptom-detected breast cancer (46% and 49%), and stage III diagnosis (7% and 7%). In multivariable models adjusting for age and year of diagnosis, race, BMI, Charlson comorbidity score and depression diagnosis no differences were observed in the outcomes by presence of diabetes. Further investigation is warranted to determine how diabetes acts as a mediating factor in adverse breast cancer outcomes.

BACKGROUND AND PURPOSE: Resistance to endocrine therapies in hormone receptor (HR)-positive breast cancer is a significant challenge. Prior studies have shown that low-dose oral cyclophosphamide can transiently deplete regulatory T cells (Tregs) and improve anti-tumor immunity. We investigated the combination of exemestane with cyclophosphamide in patients with advanced HR-positive breast cancer and assessed changes in circulating immune cell subsets. METHODS: This was a single-arm phase II trial of exemestane with cyclophosphamide in patients with metastatic HR-positive/HER2-negative breast cancer who had progressed on prior endocrine therapy (ClinicalTrials.gov: NCT01963481). Primary endpoint was progression-free survival (PFS) at 3 months (RECIST 1.1). Secondary objectives included median PFS, objective response rate, duration of response, and safety. Circulating Tregs (FOXP3+Helios+) and other immune cell subsets were monitored during treatment and compared with healthy controls. RESULTS: Twenty-three patients were enrolled. Treatment was well tolerated, without grade 4/5 toxicities. Objective responses were seen in 6/23 patients (26.1%; 95% CI 10.2-48.4%) and were durable (median 11.6 months). Three-month PFS rate was 50.1% (95% CI 33.0-76.0%); median PFS was 4.23 months (95% CI 2.8-11.7). No treatment-related decrease in Tregs was observed. However, elevated baseline levels of Naive Tregs [greater than 2.5 (the median of the naive Tregs)] were associated with relative risk of disease progression or death [hazard ratio 11.46 (95% CI 2.32-56.5)]. In addition, the baseline levels of Naive Tregs (adj-p = 0.04), Memory Tregs (adj-p = 0.003), CD4 + Central Memory T cells (adj-p = 0.0004), PD-1 + CD4 + Central Memory T cells (adj-p = 0.008), and PD-1 + CD4 + Effector Memory T cells (adj-p = 0.009) were significantly greater in the patients than in the healthy controls; the baseline levels of %CD4 + Naive T cells (adj-p = 0.0004) were significantly lower in patients compared with healthy controls (n = 40). CONCLUSION: Treg depletion was not observed with low-dose cyclophosphamide when assessed by the specific marker FOXP3 + Helios +; however, baseline naive Tregs were associated with 3-month PFS. Exemestane/cyclophosphamide combination had favorable safety profile with evidence of clinical activity in heavily pretreated patients.

PURPOSE: To report a case of neovascular and angle closure glaucoma secondary to breast cancer metastatic to the iris that was successfully treated with injections of intravitreal bevacizumab (Avastin) 1.25 mg/0.05 mL. METHODS: Case report. PATIENTS: A 47-year-old woman with metastatic breast cancer presented to The New York Eye Cancer Center with left ocular pain, photosensitivity, vision loss, and multiple iris nodules. Her intraocular pressure was uncontrolled. Gonioscopy revealed neovascularization of the iris and angle; no choroidal neovascularization was noted. Ultrasound biomicroscopy demonstrated tumor invasion of iris stroma with marked anterior uveal thickening and narrowed angles. RESULTS: Three monthly injections of intravitreal bevacizumab resulted in nearly complete resolution of iris neovascularization, reduction of intraocular pressure, and control of tumor (although a small amount of residual tumor remained). CONCLUSION: Intravitreal anti-vascular endothelial growth factor therapy for breast cancer metastatic to the iris with secondary neovascular glaucoma provided good local control for a limited follow-up period, because the patient died because of systemic complications of her disease.