Breast Cancer Screening, Diagnosis, and Surgery during the Pre- and Peri-pandemic: Experience of Patients in a Statewide Health Information Exchange.

BACKGROUND: Measures taken to address the COVID-19 pandemic interrupted routine diagnosis and care for breast cancer. The aim of this study was to characterize the effects of the pandemic on breast cancer care in a statewide cohort. PATIENTS AND METHODS: Using data from a large health information exchange, we retrospectively analyzed the timing of breast cancer screening, and identified a cohort of newly diagnosed patients with any stage of breast cancer to further access the information available about their surgical treatments. We compared data for four subgroups: pre-lockdown (preLD) 25 March to 16 June 2019; lockdown (LD) 23 March to 3 May 2020; reopening (RO) 4 May to 14 June 2020; and post-lockdown (postLD) 22 March to 13 June 2021. RESULTS: During LD and RO, screening mammograms in the cohort decreased by 96.3% and 36.2%, respectively. The overall breast cancer diagnosis and surgery volumes decreased up to 38.7%, and the median time to surgery was prolonged from 1.5 months to 2.4 for LD and 1.8 months for RO. Interestingly, higher mean DCIS diagnosis (5.0 per week vs. 3.1 per week, p < 0.05) and surgery volume (14.8 vs. 10.5, p < 0.05) were found for postLD compared with preLD, while median time to surgery was shorter (1.2 months vs. 1.5 months, p < 0.0001). However, the postLD average weekly screening and diagnostic mammogram did not fully recover to preLD levels (2055.3 vs. 2326.2, p < 0.05; 574.2 vs. 624.1, p < 0.05). CONCLUSIONS: Breast cancer diagnosis and treatment patterns were interrupted during the lockdown and still altered 1 year after. Screening in primary care should be expanded to mitigate possible longer-term effects of these interruptions.

Advantages of the Delayed-Immediate Microsurgical Breast Reconstruction: Extending the Choice.

BACKGROUND: Deep inferior epigastric perforator (DIEP) reconstruction can be performed in an immediate (at time of mastectomy), delayed-immediate (immediate tissue expander followed by staged DIEP), or delayed timing following mastectomy. Avoiding flap radiation is a known benefit of the delayed-immediate approach. The purpose of this study is to evaluate patients who chose DIEP flap as the reconstructive method during initial consultation and compared characteristics of surgery in relation to their final reconstructive choice. METHODS: Consecutive patients having breast reconstruction from 2017 to 2019 were divided into three groups: immediate DIEP after mastectomy (Group I); delayed-immediate DIEP with tissue expander first followed by DIEP (Group II); and patients who initially chose delayed-immediate DIEP but later decided on implants for the second stage of reconstruction (Group III). Exclusion criteria were patients that had delayed DIEP (no immediate reconstruction) or had initially chose implant-based reconstruction. RESULTS: The study included 59 patients. Unilateral free flaps in Group II had shorter operative times (318 minutes) compared with Group I unilateral free flaps (488 minutes) (p = 0.024). Eleven patients (30.6%) had prophylactic mastectomies in Group I compared with none in Group II (p = 0.004). Patients who had immediate tissue expansion frequently changed their mind from DIEP to implant for second stage reconstruction frequently (52.2%). CONCLUSION: Delayed-immediate DIEP reconstruction has several advantages over immediate DIEP flap including shorter free flap operative times. Patients commonly alter their preference for second stage reconstruction. A patient-centered advantage of delayed-immediate reconstruction is prolonging the time for patients to make their choice for the final reconstruction.

Bankruptcy among insured surgical patients with breast cancer: Who is at risk?

BACKGROUND: The rising cost of cancer treatment has been linked to higher bankruptcy rates and worse mortality among patients with cancer. The objective of this study was to identify the characteristics of insured patients with breast cancer who underwent surgery and filed for bankruptcy. METHODS: Insured patients with breast cancer who underwent surgery were identified in the Indiana State Cancer Registry (ISCR) from January 1, 2008 to December 31, 2014. Patients who filed for Chapter 7 or 13 bankruptcy in the Public Access to Courts Electronic Records (PACER) database were linked to patients in the ISCR. The cohort was divided into 2 groups: no bankruptcy (NB) and bankruptcy after diagnosis (BAD). Bivariate analysis and a logistic regression model were used to identify patients who were at increased risk of filing for bankruptcy after their diagnosis. RESULTS: Of 23,012 patients, 207 (0.9%) filed for bankruptcy after diagnosis and 22,805 (99.1%) did not file for bankruptcy. The patients who filed for bankruptcy after diagnosis were younger (BAD vs NB: median age, 53 years [interquartile range (IQR), 46-61 years] vs 62 years [IQR, 52-71 years], non-White (BAD vs NB, 20.5% vs 8.5%), and lived in lower income neighborhoods (BAD vs NB: median annual income, $50,869 [IQR, $41,051-$61,150] vs $52,522 [IQR, $41,356-$64,915]). On multivariable analysis, younger age (aged ≤40 years: odds ratio [OR], 5.41; 95% CI, 2.8-12.31; aged 41-64 years: OR, 2.65; 95% CI, 1.33-5.12; aged ≥65 years, reference category) and non-White race (non-White: OR, 2.43; 95% CI, 1.54-3.83; White, reference category) were associated with filing for bankruptcy after diagnosis CONCLUSIONS: Younger age and non-White race are associated with an increased risk of filing for bankruptcy after diagnosis among insured patients who undergo surgery for breast cancer. Additional steps should be taken to screen and address the financial vulnerability of these patients at treatment initiation.

Immediate Lymphatic Reconstruction after Axillary Lymphadenectomy: A Single-Institution Early Experience.

PURPOSE: Lymphedema is progressive arm swelling from lymphatic dysfunction which can occur in 30% patients undergoing axillary dissection/radiation for breast cancer. Immediate lymphatic reconstruction (ILR) is performed in an attempt decrease the risk of lymphedema in patients undergoing axillary lymph node dissection (ALND). The purpose of this study was to assess the efficacy of ILR in preventing lymphedema rates in ALND patients. METHODS: An institutional review board-approved retrospective review was performed of all patients who underwent ILR from 2017 to 2019. Patient demographics, comorbidities, operative and pathologic findings, number of LVAs, limb measurements, complications, and follow-up were recorded and analyzed. Student's sample t-test, Fisher's exact test, and ANOVA were used to analyze data; significance was set at p < 0.05. RESULTS: Thirty-three patients were included in this analysis. Three patients (9.1%) developed persistent lymphedema, and two patients (6.1%) developed transient arm edema that resolved with compression and massage therapy. A significant effect was found for body mass index and the number of lymph nodes taken on the development of lymphedema (p < 0.01). CONCLUSIONS: The rate of lymphedema in this series was 9.1%, which is an improvement from historical rates of lymphedema. Our findings support ILR as a technique that potentially decreases the incidence of lymphedema after axillary lymphadenectomy. Obesity and number of lymph nodes removed were significant predictive variables for the development of lymphedema following LVA.

The Landmark Series: Axillary Management in Breast Cancer.

The evolution in axillary management for patients with breast cancer has resulted in multiple dramatic changes over the past several decades. The end result has been an overall deescalation of surgery in the axilla. Landmark trials that have formed the basis for the current treatment guidelines are reviewed herein.

Breast Cancer Presentation, Surgical Management and Mortality Across the Rural-Urban Continuum in the National Cancer Database.

OBJECTIVE: The purpose of this study was to examine differences in presentation, surgical management, and mortality among breast cancer patients in the National Cancer Database (NCDB) based on area of residence. METHODS: The NCDB was queried for women with a diagnosis of breast cancer from 1 January 2004-31 December 2015. The data were divided by metropolitan (large, medium, small) and non-metropolitan (urban, rural) status. RESULTS: Cancer stage increased with rurality (p < 0.0001). Residency in a large metropolitan area was associated with increased breast reconstruction rates (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.19-1.30) and reduced overall mortality (hazard ratio 0.92, 95% CI 0.89-0.95) compared with rural areas. There was no difference in mastectomy use among small metropolitan (OR 1.03, 95% CI 1.01-1.04), urban (OR 0.99, 95% CI 0.98-1), and rural areas (OR 1.05, 95% CI 1.01-1.07) compared with large metropolitan areas. CONCLUSIONS: Across the rural-urban continuum in the NCDB, stage of cancer presentation increased with rurality. Conversely, residency in a large metropolitan area was associated with higher reconstruction rates and a reduction in overall mortality. Future studies should evaluate factors contributing to advanced disease presentation and lower reconstruction rates among rural breast cancer patients.

A Systematic Review of Utility Score Assessments in the Breast Surgery Cost-Analysis Literature.

BACKGROUND: Surgery for breast cancer can have significant impact on patient quality-of-life. Cost-utility analysis provides a way to analyze the economic impact of a surgical procedure with the change in a patient's quality of life. Utility scores are used in these analyses to quantify the impact on quality of life. We undertook a systematic review of the literature on breast cancer surgical procedures to compile a repository of utility scores and to assess gaps in the current literature. METHODS: Following PRISMA guidelines, a systematic review was performed for studies reporting utility scores for breast surgery and breast reconstruction. The health states and utility scores were extracted and grouped into seven procedural categories based on oncologic and reconstructive methods. Mean utility score and ranges were calculated and reported for each procedural category. RESULTS: Nineteen articles met the inclusion criteria assessing 118 health states. Most utility scores were obtained from healthcare professionals. Breast-conserving therapy yielded the highest mean utility score at 0.79, whereas mastectomy yielded a mean utility score of 0.75. Among reconstruction health states, implant reconstruction had a lower score than autologous reconstruction (0.64 implant vs. latissimus dorsi 0.69 and TRAM/DIEP 0.71). No utility scores were found associated with oncoplasty or nipple-sparing mastectomy procedures. CONCLUSIONS: A reliable body of utility scores is important in enabling future cost-utility and value-based analysis comparisons for breast surgical oncology. Additional work is needed to obtain health state assessments from the patient perspective, as well as assessment of more modern surgical and reconstructive approaches.

The impact of preoperative magnetic resonance imaging and lumpectomy cavity shavings on re-excision rate in pure ductal carcinoma in situ-A single institution's experience.

BACKGROUND AND OBJECTIVES: The impact of preoperative magnetic resonance imaging (pMRI) and cavity shave margins (CSM) on re-excision rate (RR) in DCIS is unclear. We investigated whether either modality was associated with RR in DCIS. METHODS: This is a single-institution retrospective study of 295 women undergoing breast conservation surgery for pure DCIS (2010-2013). CSM were the systematic resection of 4-6 margins during lumpectomy whereas selective shave margins (SSM) were the selective resection of 1-3 margins. Patient demographics and clinical characteristics were abstracted. RR was analyzed according to the use of pMRI, SSM, or CSM with respect to three high-volume breast surgeons at our institution. RESULTS: RR was not associated with the use of pMRI (P = 0.87). Any shave margins (P = 0.05), DCIS size (P < 0.001), and DCIS grade (P = 0.14) associated with a lower RR. Of our high-volume surgeons, RR was lower for Surgeon A (P = 0.02). Multivariate analyses showed larger DCIS (OR 1.35, P = 0.005) and practices specific to surgeons B (OR 3.23, P = 0.04) and C (OR 3.57, P = 0.04) increased re-excision odds. CONCLUSIONS: SSM/CSM and pMRI use varied among surgeons. Our results suggested the routine use of CSM, not pMRI, could lower re-excision rate, which highlighted a quality improvement opportunity at our institution.

Quality of life and sexual well-being after nipple sparing mastectomy: A matched comparison of patients using the breast Q.

BACKGROUND: Nipple sparing mastectomy (NSM) is considered safe for select patients. Our objective was to examine quality of life (QOL) and satisfaction for NSM compared with skin sparing mastectomy (SSM). We aimed to evaluate these using the BREAST-Q. METHODS: After IRB approval, we analyzed patients who underwent NSM and reconstruction between July 2010-June 2015. NSM patients were matched with those after SSM based on age, race, and body mass index. Telephone interviews were prospectively conducted using the BREAST-Q Mastectomy Postoperative Module. Bivariate analysis and a paired samples t-test were performed. RESULTS: We identified 43 patients meeting our inclusion criteria with a response rate 60% (N = 26). NSM and SSM patients were matched well in age (P = 1.00), race (P = 1.00), and Body Mass Index (P = 0.99). There were no significant differences in stage, estrogen and progesterone status, HER2 expression, reconstruction type and radiation. Mean BREAST-Q scores did not vary between NSM and SSM in regards to satisfaction with breasts (P = 0.604), psychosocial well-being (P = 0.146), physical well-being (P = 0.121), and satisfaction with surgeon (P = 0.170). Sexual well-being was significantly higher in NSM patients (P = 0.011). CONCLUSION: NSM provides patients with favorable results in psychosocial, sexual, and physical well-being and overall satisfaction. Sexual well-being showed significant improvement for NSM.

Loss of Anti-HER-3 CD4+ T-Helper Type 1 Immunity Occurs in Breast Tumorigenesis and is Negatively Associated with Outcomes.

BACKGROUND: We previously demonstrated a progressive loss of the anti-human epidermal growth factor receptor 2 (HER2) CD4+ T-helper type 1 (Th1) response during HER2pos breast tumorigenesis. This loss is associated with residual disease following neoadjuvant therapy and increased risk of recurrence. In this study, we assessed the fate of anti-HER3 Th1 immunity during breast tumorigenesis. METHODS: Peripheral blood from 131 subjects, including healthy donors (HDs), patients with benign breast disease (BD), ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC), was collected. Interferon (IFN)-γpos immune responses to four HER3-derived major histocompatibility complex (MHC) class II promiscuous peptides were tested via enzyme-linked immunosorbent (ELISPOT) assays, and three immune response parameters were compared: anti-HER3 (i) responsivity, or proportion of subjects responding to at least one peptide; (ii) repertoire, or number of responding peptides; and (iii) cumulative response, or summed peptide response. RESULTS: A significant decline in anti-HER3 Th1 response was observed going from HDs to IBC patients; patients with triple-negative breast cancer (TNBC) demonstrated the lowest responses. HDs had significantly higher Th1 responses versus estrogen receptor (ER)pos IBC and TNBC patients across all three immune parameters; HER2pos IBC patients displayed responses similar to HDs and BDs. Patients with recurrent breast cancer and residual disease following neoadjuvant therapy demonstrated significantly lower anti-HER3 Th1 immunity compared with patients without recurrence or with a pathologic complete response to neoadjuvant therapy. CONCLUSIONS: Anti-HER3 CD4+ Th1 responses decline during breast tumorigenesis, particularly in TNBC. Attempts to immunologically restore depressed responses in vulnerable subgroups may help mitigate recurrence.

Evaluating the Risk of Upstaging HER2-Positive DCIS to Invasive Breast Cancer.

BACKGROUND: Overexpression of human epidermal growth factor 2 (HER2) in invasive breast cancer (IBC) is an independent poor prognostic factor. However, the significance of HER2 overexpression in ductal carcinoma in situ (DCIS) is not well defined. The current study assessed the correlation of HER2+ DCIS with the rate of upstaging to IBC on the final pathology. METHODS: The study retrospectively analyzed patients with the diagnosis of DCIS on core needle biopsy (CNB) at the authors' institution from 2009 to 2016. Data were analyzed using two-sample t tests. Multivariate analysis was performed using logistic regression. RESULTS: The study found that HER2+ DCIS had significantly higher rates of upstaging to IBC than HER2- DCIS (odds ratio [OR] 1.89; p = 0.012). In addition, triple-positive disease was more than two times more likely to be upstaged (OR 2.5; p = 0.01), whereas patients with estrogen (ER)-positive, progesterone (PR)-positive, and HER2- diseases were half as likely to be upstaged (OR 0.5; p = 0.04). Upstaging did not differ for patients with triple-negative disease (OR 0.89; p = 0.8). Additionally, patients with HER2+ DCIS were significantly younger regardless of ER/PR status (p = 0.03). The overexpression of HER2 in patients with an initial diagnosis of DCIS on CNB were twice as likely to have IBC on the final pathology as those who did not. CONCLUSION: The results suggest that overexpression of HER2 may serve as a biomarker for risk stratification of patients with DCIS and may help to guide treatment strategies in the future. For institutions in which HER2 testing may be performed on DCIS, patients should be counseled appropriately about the risk of upgrade to IBC.

Anti-HER2 CD4+ T-Helper Type 1 Immune Response is Superior to Breast MRI for Assessing Response to Neoadjuvant Therapy in Patients with HER2-Positive Breast Cancer.

BACKGROUND: In human epidermal growth factor 2-positive breast cancer (HER2+BC), neoadjuvant chemotherapy and anti-HER2-targeted therapy (nCT) achieves a complete pathologic response (pCR) in 40-67% of patients. Posttreatment magnetic resonance imaging (pMRI) is considered the gold standard, with high specificity but lower sensitivity for assessing response. The authors previously determined that anti-HER2Th1 immune response is associated with pathologic response after nCT in HER2+BC patients. This study contrasted pMRI with anti-HER2Th1 response for assessing pCR in HER2+BC. METHODS: A retrospective review of HER2+BC patients at the authors' institution was performed. Original pMRI reports were collected, and images were reviewed by a breast radiologist blinded to pCR and immune response. The post-nCT imaging-based tumor response was assessed by Response Evaluation Criteria in Solid Tumors. The anti-HER2Th1 response was determined by ex vivo stimulation of peripheral blood mononuclear cells with six major histocompatibility complex (MHC) class 2-derived HER2 peptides via enzyme-linked immunospot (ELISPOT). Posttreatment MRI and anti-HER2Th1 responses were cross-tabulated with pCR. Standard diagnostic metrics were computed. RESULTS: For 30 patients, pMRI and anti-HER2Th1 immune response were measured, with 13 patients (43.3%) achieving pCR. The mean anti-HER2Th1 response in pCR was 167 (range 53-418), and

Outcomes After Oncoplastic Breast-Conserving Surgery in Breast Cancer Patients: A Systematic Literature Review.

BACKGROUND: Surgeons have increasingly performed breast-conserving surgery (BCS) utilizing oncoplastic techniques in place of standard lumpectomy for early-stage breast cancer. We assess oncologic outcomes after oncoplastic BCS for T1-T2 breast cancer. METHODS: A systematic literature review identified peer-reviewed articles in PubMed evaluating BCS with oncoplastic reconstruction. Selected studies reported on positive margin rate (PMR), re-excision rate (RR), conversion to mastectomy rate (CMR), overall survival (OS), disease-free survival (DFS), local recurrence (LR), distant recurrence (DR), complication rate, and/or cosmetic outcomes. RESULTS: The search yielded 474 articles; 55 met the inclusion criteria and collectively evaluated 6011 patients with a mean age 54.6 years over a mean follow-up 50.5 months. T1 (43.8 %) and T2 (39.3 %) invasive ductal carcinoma were the most common tumor histopathologies. PMR, RR, and CMR were 10.8, 6.0, and 6.2 %, respectively, while OS, DFS, LR and DR were 95.0, 90.0, 3.2, and 8.7 %, respectively. Margin widths were heterogeneously defined in studies that included margin assessment. The PMR was not significantly different when positive margins were defined as tumor <10, <5, < 2, and <1 mm from ink margin, or tumor on ink (p = 0.162). Eleven studies reported specific margins for 1455 patients, of whom 143 (9.8 %) had positive margins, including 113 (7.8 %) with tumor on ink. CONCLUSIONS: This study is the largest comprehensive literature review to date on oncoplastic BCS. Our systematic review reveals high rates of OS and DFS with low LR, DR, PMR, RR, CMR and complication rates, thereby confirming the oncologic safety of this procedure in patients with T1-T2 invasive breast cancer.

Lifestyle risk factors associated with arm swelling among women with breast cancer.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a feared complication for breast cancer patients who have undergone axillary surgery. Although clinical risk factors for BCRL are defined, data are sparse regarding common exposures that might induce incident arm swelling. The goal of this study was to quantify the association between common exposures thought to be potential risk factors and the occurrence of incident arm swelling among breast cancer survivors with or at risk for BCRL. METHODS: This is a prospective subanalysis of the Physical Activity and Lymphedema (PAL) trial, a randomized controlled trial of 295 breast cancer survivors. Participants reported their exposure to 30 different potential risk factors at 3 month intervals for 1 year. Incident arm swelling was defined as a ≥5% increase in interlimb water volume difference between two consecutive time points. RESULTS: Twenty-seven participants (9%) experienced incident arm swelling and 268 patients (91%) did not. Sauna use was the only exposure that was significantly predictive of incident arm swelling (p = 0.05). Nonwhite and nonblack participants had a significantly increased risk for experiencing incident arm swelling (p = 0.005 for both comparisons). CONCLUSIONS: In our patient cohort, many common exposures that have been reported to be risk factors did not prove to have a significant predictive relationship for incident arm swelling. This study supports the recommendation that breast cancer patients who have had axillary surgery should avoid sauna use. The results do not confirm the need for other restrictions that may interfere with the quality of life in women with breast cancer.

The no-vertical scar technique for oncoplastic breast reconstruction.

INTRODUCTION: Oncoplastic reconstruction can optimize breast conserving therapy. Nipple loss is a concern in patients with significant ptosis and breast hypertrophy particularly with pedicle undermining during tumor resection. The modified Robertson technique (No-Vertical Scar reduction) has been previously described for breast reduction in large, ptotic patients using a wide, bell-shaped inferior pedicle with only inframammary fold and peri­areolar incisions. The purpose of this study was to evaluate the No-Vertical Scar (NVS) technique applied to oncoplastic reconstruction. METHODS: Women undergoing oncoplastic breast reduction using a NVS, Wise, or Vertical method were assessed. Predictive variables included patient demographics, comorbidities, and sternal notch to nipple (SNN) distance. Outcome variables were delayed wound healing, surgical site infection, seroma, fat necrosis, nipple necrosis, use of a free nipple graft, and time between surgery and adjuvant radiation. RESULTS: Fifty patients met inclusion criteria using NVS (N = 15), Wise (N = 16), and Vertical (N = 19) methods. The NVS group had a significantly higher BMI (p=.009), greater sternal notch to nipple distance (p=<0.001) and increased resection volume (p=<0.001) as compared to Wise and Vertical groups. There was no significant difference in complications (p=.25). No nipple necrosis occurred, and no free nipple grafts were required. CONCLUSION: The NVS approach is a useful technique for oncoplastic reconstruction in select patients with macromastia and severe Grade II or Grade III ptosis. The wide, bell-shaped pedicle is versatile for obliterating a lumpectomy cavity and optimizing nipple perfusion if pedicle undermining occurs during resection.