Reexamining Time From Breast Cancer Diagnosis to Primary Breast Surgery.

Importance: Although longer times from breast cancer diagnosis to primary surgery have been associated with worse survival outcomes, the specific time point after which it is disadvantageous to have surgery is unknown. Identifying an acceptable time to surgery would help inform patients, clinicians, and the health care system. Objective: To examine the association between time from breast cancer diagnosis to surgery (in weeks) and overall survival and to describe factors associated with surgical delay. The hypothesis that there is an association between time to surgery and overall survival was tested. Design, Setting, and Participants: This was a case series study that used National Cancer Database (NCDB) data from female individuals diagnosed with breast cancer from 2010 to 2014 (with 5-year follow-up to 2019). The NCDB uses hospital registry data from greater than 1500 Commission on Cancer-accredited facilities, accounting for 70% of all cancers diagnosed in the US. Included participants were females 18 years or older with stage I to III ductal or lobular breast cancer who underwent surgery as the first course of treatment. Patients with prior breast cancer, missing receptor information, neoadjuvant or experimental therapy, or who were diagnosed with breast cancer on the date of their primary surgery were excluded. Multivariable Cox regression was used to evaluate factors associated with overall survival. Patients were censored at death or last follow-up. Covariates included age and tumor characteristics. Multinomial regression was performed to identify factors associated with longer time to surgery, using surgery 30 days or less from diagnosis as the reference group. Data were analyzed from March 15 to July 7, 2022. Exposures: Time to receipt of primary breast surgery. Measures: The primary outcome measure was overall survival. Results: The final cohort included 373 334 patients (median [IQR] age, 61 [51-70] years). On multivariable Cox regression analysis, time to surgery 9 weeks (57-63 days) or later after diagnosis was associated with worse overall survival (hazard ratio, 1.15; 95% CI, 1.08-1.23; P < .001) compared with surgery between 0 to 4 weeks (1-28 days). By multinomial regression, factors associated with longer times to surgery (using surgery 1-30 days from diagnosis as a reference) included the following: (1) younger age, eg, the adjusted odds ratio (OR) for patients 45 years or younger undergoing surgery 31 to 60 days from diagnosis was 1.32 (95% CI, 1.28-1.38); 61 to 74 days, 1.64 (95% CI, 1.52-1.78); and greater than 74 days, 1.58 (95% CI, 1.46-1.71); (2) uninsured or Medicaid status, eg, the adjusted OR for patients with Medicaid undergoing surgery 31 to 60 days from diagnosis was 1.35 (95% CI, 1.30-1.39); 61 to 74 days, 2.13 (95% CI, 2.01-2.26); and greater than 74 days, 3.42 (95% CI, 3.25-3.61); and (3) lower neighborhood household income, eg, the adjusted OR for patients with household income less than $38,000 undergoing surgery 31 to 60 days from diagnosis was 1.35 (95% CI, 1.02-1.07); 61 to 74 days, 1.21 (95% CI, 1.15-1.27); and greater than 74 days, 1.53 (95% CI, 1.46-1.61). Conclusions and Relevance: Findings of this case series study suggest the use of 8 weeks or less as a quality metric for time to surgery. Time to surgery of greater than 8 weeks may partly be associated with disadvantageous social determinants of health.

Analysis of the Impact of the COVID-19 Pandemic on the Multidisciplinary Management of Breast Cancer: Review from the American Society of Breast Surgeons COVID-19 and Mastery Registries.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in rapid and regionally different approaches to breast cancer care. METHODS: In order to evaluate these changes, a COVID-19-specific registry was developed within the American Society of Breast Surgeons (ASBrS) Mastery that tracked whether decisions were usual or modified for COVID-19. Data on patient care entered into the COVID-19-specific registry and the ASBrS Mastery registry from 1 March 2020 to 15 March 2021 were reviewed. RESULTS: Overall, 177 surgeons entered demographic and treatment data on 2791 patients. Mean patient age was 62.7 years and 9.0% (252) were of African American race. Initial consultation occurred via telehealth in 6.2% (173) of patients and 1.4% (40) developed COVID-19. Mean invasive tumor size was 2.1 cm and 17.8% (411) were node-positive. In estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) disease, neoadjuvant endocrine therapy (NET) was used as the usual approach in 6.9% (119) of patients and due to COVID-19 in an additional 31% (542) of patients. Patients were more likely to receive NET due to COVID-19 with increasing age and if they lived in the Northeast or Southeast (odds ratio [OR] 1.1, 2.3, and 1.7, respectively; p < 0.05). Genomic testing was performed on 51.5% (781) of estrogen-positive patients, of whom 20.7% (162) had testing on the core due to COVID-19. Patients were less likely to have core biopsy genomic testing due to COVID-19 if they were older (OR 0.89; p = 0.01) and more likely if they were node-positive (OR 4.0; p < 0.05). A change in surgical approach due to COVID-19 was reported for 5.4% (151) of patients. CONCLUSION: The ASBrS COVID-19 registry provided a platform for monitoring treatment changes due to the pandemic, highlighting the increased use of NET.

Quantitative assessment of distant recurrence risk in early stage breast cancer using a nonlinear combination of pathological, clinical and imaging variables.

Use of genomic assays to determine distant recurrence risk in patients with early stage breast cancer has expanded and is now included in the American Joint Committee on Cancer staging manual. Algorithmic alternatives using standard clinical and pathology information may provide equivalent benefit in settings where genomic tests, such as OncotypeDx, are unavailable. We developed an artificial neural network (ANN) model to nonlinearly estimate risk of distant cancer recurrence. In addition to clinical and pathological variables, we enhanced our model using intraoperatively determined global mammographic breast density (MBD) and local breast density (LBD). LBD was measured with optical spectral imaging capable of sensing regional concentrations of tissue constituents. A cohort of 56 ER+ patients with an OncotypeDx score was evaluated. We demonstrated that combining MBD/LBD measurements with clinical and pathological variables improves distant recurrence risk prediction accuracy, with high correlation (r = 0.98) to the OncotypeDx recurrence score.

Breast Cancer Found Incidentally After Reduction Mammaplasty in Young Insured Women.

BACKGROUND: Reduction mammaplasty is a common operation performed for healthy women. The estimated incidence of breast cancer diagnosed at the time of reduction mammaplasty varies from 0.06 to 4.5%, and information on the care of these patients is limited. This study aimed to determine the incidence of breast cancer identified incidentally during reduction mammaplasty and to characterize preoperative imaging. METHODS: Women 18 years of age or older who underwent reduction mammaplasty from 2013 to 2015 were identified from the Truven Health MarketScan® Research Databases. Patients with prior breast cancer were excluded. Descriptive statistics were calculated for patient characteristics, incidental breast cancer, preoperative breast imaging, and postoperative treatment. RESULTS: Reduction mammaplasty was performed for 18,969 women with a mean age of 42.5 years. Of these patients, 186 (0.98%) were incidentally found to have breast cancer, with 134 (0.71%) having invasive breast cancer and 52 (0.27%) having carcinoma in situ. The patients with incidentally found cancer were older than the patients without cancer (50.8 vs. 42.5 years; p < 0.001). Overall, 58.2% of the patients had undergone mammography before reduction mammoplasty. The rates were higher (> 80%) for the patients older than 40 years. Preoperative mammography was performed for 76.3% of those with a diagnosis of breast cancer at time of reduction mammoplasty. CONCLUSIONS: Breast cancer diagnosed incidentally at the time of reduction mammaplasty is uncommon and often radiographically occult. The majority of women older than 50 years appropriately received preoperative mammography. These data can be used to manage patient expectations about the potential for the incidental diagnosis of breast cancer at reduction mammaplasty, even with a negative preoperative mammography.

Variation in coordination of care reported by breast cancer patients according to health literacy.

BACKGROUND: Health literacy is the ability to perform basic reading and numerical tasks to function in the healthcare environment. The purpose of this study is to describe how health literacy is related to perceived coordination of care reported by breast cancer patients. METHODS: Data were retrieved from the Patient-Centered Outcomes Research Institute-sponsored "Share Thoughts on Breast Cancer" Study including demographic factors, perceived care coordination and responsiveness of care, and self-reported health literacy obtained from a mailed survey completed by 62% of eligible breast cancer survivors (N = 1221). Multivariable analysis of variance was used to characterize the association between presence of a single healthcare professional that coordinated care ("care coordinator") and perceived care coordination, stratified by health literacy level. RESULTS: Health literacy was classified as low in 24% of patients, medium in 34%, and high in 42%. Women with high health literacy scores were more likely to report non-Hispanic white race/ethnicity, private insurance, higher education and income, and fewer comorbidities (all p < 0.001). The presence of a care coordinator was associated with 17.1% higher perceived care coordination scores among women with low health literacy when compared to those without a care coordinator, whereas a coordinator modestly improved perceived care coordination among breast cancer survivors with medium (6.9%) and high (6.2%) health literacy. CONCLUSION: The use of a single designated care coordinator may have a strong influence on care coordination in patients with lower levels of health literacy.

Socioeconomic Factors Associated with Post-Mastectomy Immediate Reconstruction in a Contemporary Cohort of Breast Cancer Survivors.

BACKGROUND: Post-mastectomy reconstruction is a critical component of high-quality breast cancer care. Prior studies demonstrate socioeconomic disparity in receipt of reconstruction. Our objective was to evaluate trends in receipt of immediate reconstruction and examine socioeconomic factors associated with reconstruction in a contemporary cohort. METHODS: Using the National Cancer Database, we identified women <75 years of age with stage 0-1 breast cancer treated with mastectomy (n = 297,121). Trends in immediate reconstruction rates (2004-2013) for the overall cohort and stratified by socioeconomic factors were examined using Join-point regression analysis, and annual percentage change (APC) was calculated. We then restricted our sample to a contemporary cohort (2010-2013, n = 145,577). Multivariable logistic regression identified socioeconomic factors associated with immediate reconstruction. Average adjusted predicted probabilities of receiving reconstruction were calculated. RESULTS: Immediate reconstruction rates increased from 27 to 48%. Although absolute rates of reconstruction for each stratification group increased, similar APCs across strata led to persistent gaps in receipt of reconstruction. On multivariable logistic regression using our contemporary cohort, race, income, education, and insurance type were all strongly associated with immediate reconstruction. Patients with the lowest predicted probability of receiving reconstruction were patients with Medicaid who lived in areas with the lowest rates of high-school graduation (Black 42.4% [95% CI 40.5-44.3], White 45.7% [95% CI 43.9-47.4]). CONCLUSIONS: Although reconstruction rates have increased dramatically over the past decade, lower rates persist for disadvantaged patients. Understanding how socioeconomic factors influence receipt of reconstruction, and identifying modifiable factors, are critical next steps towards identifying interventions to reduce disparities in breast cancer surgical care.

The Role of Intraoperative Pathologic Assessment in the Surgical Management of Ductal Carcinoma In Situ.

BACKGROUND: Re-excision surgeries for the treatment of ductal carcinoma in situ (DCIS) put a strain on patients and healthcare resources; however, intraoperative pathologic assessment of DCIS may lead to a reduction in these additional surgeries. This study examined the relationship between intraoperative pathologic assessment and subsequent operations in patients with a diagnosis of DCIS. METHODS: Surveillance, Epidemiology, and End Results-Medicare patients diagnosed with DCIS from 1999 to 2007 who initially underwent partial mastectomy, without axillary surgery, were included in this study. Use of intraoperative frozen section or touch preparation during the initial surgery was assessed. Multivariable logistic regression was used to describe the relationship between the use of intraoperative pathologic assessment and any subsequent mastectomy or partial mastectomy within 90 days of the initial partial mastectomy. RESULTS: Of 8259 DCIS patients, 3509 (43 %) required a second surgery, and intraoperative pathologic assessment was performed for 2186 (26 %). Intraoperative pathologic assessment had no statistically significant effect on whether or not a subsequent breast surgery occurred (adjusted odds ratio 1.07, 95 % confidence interval 0.95-1.21; p = 0.293). Patient residence in a rural area, tumor size ≥2 cm, and poorly differentiated tumor grade were associated with a greater likelihood of subsequent surgery, while age 80 years and older was associated with a lower likelihood of subsequent surgery. CONCLUSIONS: The use of intraoperative frozen section or touch preparation during partial mastectomy from 1999 to 2007 was not associated with a reduction in subsequent breast operations in women with DCIS. These results highlight the need to identify cost-effective tools and strategies to reduce the need for additional surgery in patients with DCIS.

Impact of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial on clinical management of the axilla in older breast cancer patients: a SEER-medicare analysis.

BACKGROUND: American College of Surgeons Oncology Group (ACOSOG) Z0011 demonstrated that eligible breast cancer patients with positive sentinel lymph nodes (SLN) could be spared an axillary lymph node dissection (ALND) without sacrificing survival or local control. Although heralded as a ''practice-changing trial,'' some argue that the stringent inclusion criteria limit the trial's clinical significance. The objective was to assess the potential impact of ACOSOG Z0011 on axillary surgical management of Medicare patients and examine current practice patterns. METHODS: Medicare beneficiaries aged C66 years with nonmetastatic invasive breast cancer diagnosed from 2001 to 2007 were identified from the Surveillance, Epidemiology and End Results-Medicare database (n = 59,431). Eligibility for ACOSOG Z0011 was determined: SLN mapping, tumor\5 cm, no neoadjuvant treatment, breast conservation; number of positive nodes was determined. Actual surgical axillary management for eligible patients was assessed. RESULTS: Twelve percent (6,942/59,431) underwent SLN mapping and were node positive. Overall, 2,637 patients (4.4 % (2,637/59,431) of the total cohort, but 38 % (2,637/6,942) of patients with SLN mapping and positive nodes) met inclusion criteria for ACOSOG Z0011, had 1 or 2 positive lymph nodes, and could have been spared an ALND. Of these 2,637 patients, 46 % received a completion ALND and 54 % received only SLN biopsy. CONCLUSIONS: Widespread implementation of ACOSOG Z0011 trial results could potentially spare 38 % of older breast cancer patients who undergo SLN mapping with positive lymph nodes an ALND. However, 54 % of these patients are already managed with SLN biopsy alone, lessening the impact of this trial on clinical practice in older breast cancer patients.

Advancing optical imaging for breast margin assessment: an analysis of excisional time, cautery, and patent blue dye on underlying sources of contrast.

Breast conserving surgery (BCS) is a recommended treatment for breast cancer patients where the goal is to remove the tumor and a surrounding rim of normal tissue. Unfortunately, a high percentage of patients return for additional surgeries to remove all of the cancer. Post-operative pathology is the gold standard for evaluating BCS margins but is limited due to the amount of tissue that can be sampled. Frozen section analysis and touch-preparation cytology have been proposed to address the surgical needs but also have sampling limitations. These issues represent an unmet clinical need for guidance in resecting malignant tissue intra-operatively and for pathological sampling. We have developed a quantitative spectral imaging device to examine margins intra-operatively. The context in which this technology is applied (intra-operative or post-operative setting) is influenced by time after excision and surgical factors including cautery and the presence of patent blue dye (specifically Lymphazurin™, used for sentinel lymph node mapping). Optical endpoints of hemoglobin ([THb]), fat ([ß-carotene]), and fibroglandular content via light scattering (<µ(s)'>) measurements were quantified from diffuse reflectance spectra of lumpectomy and mastectomy specimens using a Monte Carlo model. A linear longitudinal mixed-effects model was used to fit the optical endpoints for the cautery and kinetics studies. Monte Carlo simulations and tissue mimicking phantoms were used for the patent blue dye experiments. [THb], [ß-carotene], and <µ(s)'> were affected by <3.3% error with <80 µM of patent blue dye. The percent change in [ß-carotene], <µ(s)'>, and [ß-carotene]/<µ(s)'> was <14% in 30 minutes, while percent change in [THb] was >40%. [ß-carotene] and [ß-carotene]/<µ(s)'> were the only parameters not affected by cautery. This work demonstrates the importance of understanding the post-excision kinetics of ex-vivo tissue and the presence of cautery and patent blue dye for breast tumor margin assessment, to accurately interpret data and exploit underling sources of contrast.

Intraoperative imprint cytology and frozen section pathology for margin assessment in breast conservation surgery: a systematic review.

BACKGROUND: Achieving negative surgical margins is critical to minimizing the risk of tumor recurrence in patients undergoing breast conservation surgery (BCS) for a breast malignancy. Our objective was to perform a systematic review comparing reexcision rates, sensitivity and specificity of the intraoperative use of the margin assessment techniques of imprint cytology (IC) and frozen section analysis (FSA), against permanent histopathologic section (PS). METHODS: The databases PubMed, Web of Knowledge, Cochrane Library and CINAHL Plus were searched for literature published from 1997 to 2011. Original investigations of patients who underwent BCS for breast cancer that evaluated margin assessment with PS and/or IC or FSA were included. Of 182 titles identified, 41 patient cohorts from 37 articles met inclusion criteria: PS (n = 19), IC (n = 7) and FSA (n = 15). Studies were summarized qualitatively using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cohort studies and the Strength of Recommendation Taxonomy (SORT) numerical scale for diagnostic studies. RESULTS: The final reexcision rates after primary BCS were 35 % for PS, 11 % for IC (p = 0.001 vs. PS) and 10 % for FSA (p < 0.0001 vs. PS). For IC, reexcision rates decreased from 26 to 4 % (p = 0.18) and for FSA, reexcision rates decreased from 27 to 6 % (p < 0.0001). The pooled sensitivity of IC and FSA were 72 and 83 %. The pooled specificity of IC and FSA were 97 and 95 %. The average length of each technique was 13 min for IC and 27 min for FSA. CONCLUSIONS: Patients who underwent BCS with intraoperative IC or FSA to assess negative surgical margins had significantly fewer secondary surgical procedures for excision of their breast malignancies.

Performance metrics of an optical spectral imaging system for intra-operative assessment of breast tumor margins.

As many as 20-70% of patients undergoing breast conserving surgery require repeat surgeries due to a close or positive surgical margin diagnosed post-operatively [1]. Currently there are no widely accepted tools for intra-operative margin assessment which is a significant unmet clinical need. Our group has developed a first-generation optical visible spectral imaging platform to image the molecular composition of breast tumor margins and has tested it clinically in 48 patients in a previously published study [2]. The goal of this paper is to report on the performance metrics of the system and compare it to clinical criteria for intra-operative tumor margin assessment. The system was found to have an average signal to noise ratio (SNR) >100 and <15% error in the extraction of optical properties indicating that there is sufficient SNR to leverage the differences in optical properties between negative and close/positive margins. The probe had a sensing depth of 0.5-2.2 mm over the wavelength range of 450-600 nm which is consistent with the pathologic criterion for clear margins of 0-2 mm. There was <1% cross-talk between adjacent channels of the multi-channel probe which shows that multiple sites can be measured simultaneously with negligible cross-talk between adjacent sites. Lastly, the system and measurement procedure were found to be reproducible when evaluated with repeated measures, with a low coefficient of variation (<0.11). The only aspect of the system not optimized for intra-operative use was the imaging time. The manuscript includes a discussion of how the speed of the system can be improved to work within the time constraints of an intra-operative setting.

Optical assessment of tumor resection margins in the breast.

Breast conserving surgery, in which the breast tumor and surrounding normal tissue are removed, is the primary mode of treatment for invasive and in situ carcinomas of the breast, conditions that affect nearly 200,000 women annually. Of these nearly 200,000 patients who undergo this surgical procedure, between 20-70% of them may undergo additional surgeries to remove tumor that was left behind in the first surgery, due to the lack of intra-operative tools which can detect whether the boundaries of the excised specimens are free from residual cancer. Optical techniques have many attractive attributes which may make them useful tools for intra-operative assessment of breast tumor resection margins. In this manuscript, we discuss clinical design criteria for intra-operative breast tumor margin assessment, and review optical techniques appied to this problem. In addition, we report on the development and clinical testing of quantitative diffuse reflectance imaging (Q-DRI) as a potential solution to this clinical need. Q-DRI is a spectral imaging tool which has been applied to 56 resection margins in 48 patients at Duke University Medical Center. Clear sources of contrast between cancerous and cancer-free resection margins were identified with the device, and resulted in an overall accuracy of 75% in detecting positive margins.

Quantitative spectral reflectance imaging device for intraoperative breast tumor margin assessment.

Diffuse reflectance spectroscopy of tissue allows quantification of underlying physiological and morphological changes associated with cancer, provided that the absorption and scattering properties of the tissue can be effectively decoupled. A particular application of interest for tissue reflectance spectroscopy in the UV-VIS is intraoperative detection of residual cancer at the margins of excised breast tumors, which could prevent costly and unnecessary repeat surgeries. Our multi-disciplinary group has developed an optical imaging device, which employs a model-based algorithm for quantification of tissue optical properties, and is capable of surveying the entire specimen surface down to a depth of 1-2 mm, all within a short time as required for intraoperative use. In an ongoing IRB-approved study, reflectance spectral images were acquired from 55 margins in 48 patients. Conversion of the spectral images to quantitative tissue parameter maps was facilitated by a fast scalable inverse Monte-Carlo model. Data from margin parameter images were reduced to image-descriptive scalar values and compared to gold-standard margin pathology. Use of a decision-tree based classification algorithm on the two most significant optical parameters resulted in a sensitivity of 79% and specificity of 67% for detection of residual tumor of all pathologic variants, with an 89% sensitivity for ductal carcinoma in situ alone. Preliminary data from this ongoing clinical study suggest that this technology could significantly reduce the number of unnecessary repeat breast conserving surgeries annually.