Postoperative radiotherapy omission in selected patients with early breast cancer following preoperative breast MRI (PROSPECT): primary results of a prospective two-arm study.

BACKGROUND: Adjuvant breast radiotherapy as a standard component of breast-conserving treatment for early cancer can overtreat many women. Breast MRI is the most sensitive modality to assess local tumour burden. The aim of this study was to determine whether a combination of MRI and pathology findings can identify women with truly localised breast cancer who can safely avoid radiotherapy. METHODS: PROSPECT is a prospective, multicentre, two-arm, non-randomised trial of radiotherapy omission in patients selected using preoperative MRI and postoperative tumour pathology. It is being conducted at four academic hospitals in Australia. Women aged 50 years or older with cT1N0 non-triple-negative breast cancer were eligible. Those with apparently unifocal cancer had breast-conserving surgery (BCS) and, if pT1N0 or N1mi, had radiotherapy omitted (group 1). Standard treatment including excision of MRI-detected additional cancers was offered to the others (group 2). All were recommended systemic therapy. The primary outcome was ipsilateral invasive recurrence rate (IIRR) at 5 years in group 1. Primary analysis occurred after the 100th group 1 patient reached 5 years follow-up. Quality-adjusted life-years (QALYs) and cost-effectiveness of the PROSPECT pathway were analysed. This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12610000810011). FINDINGS: Between May 17, 2011, and May 6, 2019, 443 patients with breast cancer underwent MRI. Median age was 63·0 years. MRI detected 61 malignant occult lesions separate from the index cancer in 48 patients (11%). Of 201 group 1 patients who had BCS without radiotherapy, the IIRR at 5 years was 1·0% (upper 95% CI 5·4%). In group 1, one local recurrence occurred at 4·5 years and a second at 7·5 years. In group 2, nine patients had mastectomy (2% of total cohort), and the 5-year IIRR was 1·7% (upper 95% CI 6·1%). The only distant metastasis in the entire cohort was genetically distinct from the index cancer. The PROSPECT pathway increased QALYs by 0·019 (95% CI 0·008-0·029) and saved AU$1980 (95% CI 1396-2528) or £953 (672-1216) per patient. INTERPRETATION: PROSPECT suggests that women with unifocal breast cancer on MRI and favourable pathology can safely omit radiotherapy. FUNDING: Breast Cancer Trials, National Breast Cancer Foundation, Cancer Council Victoria, the Royal Melbourne Hospital Foundation, and the Breast Cancer Research Foundation.

The role of surgical tissue injury and intraoperative sympathetic activation in postoperative immunosuppression after breast-conserving surgery versus mastectomy: a prospective observational study.

BACKGROUND: Breast cancer is the second most common cause of death from cancer in women worldwide. Counterintuitively, large population-based retrospective trials report better survival after breast-conserving surgery (BCS) compared to mastectomy, corrected for tumour- and patient variables. More extensive surgical tissue injury and activation of the sympathetic nervous system by nociceptive stimuli are associated with immune suppression. We hypothesized that mastectomy causes a higher expression of plasma damage associated molecular patterns (DAMPs) and more intraoperative sympathetic activation which induce postoperative immune dysregulation. Immune suppression can lead to postoperative complications and affect tumour-free survival. METHODS: In this prospective observational study, plasma DAMPs (HMGB1, HSP70, S100A8/A9 and S100A12), intraoperative sympathetic activation (Nociception Level (NOL) index from 0 to 100), and postoperative immune function (plasma cytokine concentrations and ex vivo cytokine production capacity) were compared in patients undergoing elective BCS (n = 20) versus mastectomy (n = 20). RESULTS: Ex vivo cytokine production capacity of TNF, IL-6 and IL-1ß was nearly absent in both groups one hour after surgery. Levels appeared recovered on postoperative day 3 (POD3), with significantly higher ex vivo production capacity of IL-1ß after BCS (p = .041) compared to mastectomy. Plasma concentration of IL-6 was higher one hour after mastectomy (p = .045). Concentrations of plasma alarmins S100A8/A9 and S100A12 were significantly higher on POD3 after mastectomy (p = .003 and p = .041, respectively). Regression analysis showed a significantly lower percentage of NOL measurements ≤ 8 (absence of nociception) during mastectomy when corrected for norepinephrine equivalents (36% versus 45% respectively, p = .038). Percentage of NOL measurements ≤ 8 of all patients correlated with ex vivo cytokine production capacity of IL-1ß and TNF on POD3 (r = .408; p = .011 and r = .500; p = .001, respectively). CONCLUSIONS: This pilot study revealed substantial early postoperative immune suppression after BCS and mastectomy that appears to recover in the following days. Differences between BCS and mastectomy in release of DAMPs and intraoperative sympathetic activation could affect postoperative immune homeostasis and thereby contribute to the better survival reported after BCS in previous large population-based retrospective trials. These results endorse further exploration of (1) S100 alarmins as potential therapeutic targets in breast cancer surgery and (2) suppression of intraoperative sympathetic activation to substantiate the observed association with postoperative immune dysregulation.

Selective omission of sentinel lymph node biopsy in mastectomy for ductal carcinoma in situ: identifying eligible candidates.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is recommended for patients with ductal carcinoma in situ (DCIS) undergoing mastectomy, given the concerns regarding upstaging and technical difficulties of post-mastectomy SLNB. However, this may lead to potential overtreatment, considering favorable prognosis and de-escalation trends in DCIS. Data regarding upstaging and axillary lymph node metastasis among these patients remain limited. METHODS: We retrospectively reviewed patients with DCIS who underwent mastectomy with SLNB or axillary lymph node dissection at Gangnam Severance Hospital between January 2010 and December 2021. To explore the feasibility of omitting SLNB, we assessed the rates of DCIS upgraded to invasive carcinoma and axillary lymph node metastasis. Binary Cox regression analysis was performed to identify clinicopathologic factors associated with upstaging and axillary lymph node metastasis. RESULTS: Among 385 patients, 164 (42.6%) experienced an invasive carcinoma upgrade: microinvasion, pT1, and pT2 were confirmed in 53 (13.8%), 97 (25.2%), and 14 (3.6%) patients, respectively. Seventeen (4.4%) patients had axillary lymph node metastasis. Multivariable analysis identified age ≤ 50 years (adjusted odds ratio [OR], 12.73; 95% confidence interval [CI], 1.18-137.51; p = 0.036) and suspicious axillary lymph nodes on radiologic evaluation (adjusted OR, 9.31; 95% CI, 2.06-41.99; p = 0.004) as independent factors associated with axillary lymph node metastasis. Among patients aged > 50 years and/or no suspicious axillary lymph nodes, only 1.7-2.3%) experienced axillary lymph node metastasis. CONCLUSIONS: Although underestimation of the invasive component was relatively high among patients with DCIS undergoing mastectomy, axillary lymph node metastasis was rare. Our findings suggest that omitting SLNB may be feasible for patients over 50 and/or without suspicious axillary lymph nodes on radiologic evaluation.

Association of travel time, patient characteristics, and hospital quality with patient mobility for breast cancer surgery: A national population-based study.

BACKGROUND: This national study investigated hospital quality and patient factors associated with treatment location for breast cancer surgery. METHODS: By using linked administrative data sets from the English National Health Service, the authors identified all women diagnosed between January 2, 2016, and December 31, 2018, who underwent breast-conserving surgery (BCS) or a mastectomy with or without immediate breast reconstruction. The extent to which patients bypassed their nearest hospital was investigated using a geographic information system (ArcGIS). Conditional logistic regressions were used to estimate the impact of travel time, hospital quality, and patient characteristics. RESULTS: 22,622 Of 69,153 patients undergoing BCS, 22,622 (32.7%) bypassed their nearest hospital; and, of 23,536 patients undergoing mastectomy, 7179 (30.5%) bypassed their nearest hospital. Women who were younger, without comorbidities, or from rural areas were more likely to travel to more distant hospitals (p < .05). Patients undergoing BCS (odds ratio [OR], 1.85; 95% confidence interval [CI], 1.36-2.50) or mastectomy (OR, 1.52; 95% CI, 1.14-2.02) were more likely to be treated at specialist breast reconstruction centers despite not undergoing the procedure. Patients receiving mastectomy and immediate breast reconstruction were more likely to travel to hospitals employing surgeons who had a media reputation (OR, 2.41; 95% CI, 1.28-4.52). Patients undergoing BCS were less likely to travel to hospitals with shorter surgical waiting times (OR, 0.65; 95% CI, 0.46-0.92). The authors did not observe a significant impact for research activity, hospital quality rating, breast re-excision rates, or the status as a multidisciplinary cancer center. CONCLUSIONS: Patient choice policies may drive inequalities in the health care system without improving patient outcomes.

Nonclinical factors associated with the treatment of older women with newly diagnosed low-grade ductal carcinoma in situ.

BACKGROUND: Ductal carcinoma in situ (DCIS) is the most common form of noninvasive breast cancer and is associated with an excellent prognosis. As a result, there is concern about overdiagnosis and overtreatment of DCIS because most patients with DCIS are treated as though they have invasive breast cancer and undergo either breast-conserving surgery (BCS)-most commonly followed by radiation therapy (RT)-or mastectomy. Little research to date has focused on nonclinical factors influencing treatments for DCIS. METHODS: Population-based data were analyzed from five state cancer registries (California, Florida, New Jersey, New York, and Texas) on women aged 65 years and older newly diagnosed with DCIS during the years 2003 to 2014 using a retrospective cohort design and multinominal logistic modeling. The registry records with Medicare enrollment data and fee-for-service claims to obtain treatments (BCS alone, BCS with RT, or mastectomy) were merged. Surgeon practice structure was identified through physician surveys and internet searches. RESULTS: Patients of surgeons employed by cancer centers or health systems were less likely to receive BCS with RT or mastectomy than patients of surgeons in single specialty or multispecialty practices. There also was substantial geographic variation in treatments, with patients in New York, New Jersey, and California being less likely to receive BCS with RT or mastectomy than patients in Texas or Florida. CONCLUSIONS: These findings suggest nonclinical factors including the culture of the practice and/or financial incentives are significantly associated with the types of treatment received for DCIS. Increasing awareness and targeted efforts to educate physicians about DCIS management among older women with low-grade DCIS could reduce patient harm and yield substantial cost savings.

Risk-reducing mastectomy and breast cancer mortality in women with a BRCA1 or BRCA2 pathogenic variant: an international analysis.

BACKGROUND: Risk-reducing mastectomy (RRM) is offered to women with a BRCA1 or BRCA2 pathogenic variant, however, there are limited data on the impact on breast cancer mortality. METHODS: Participants were identified from a registry of women with BRCA1/2 pathogenic variants. We used a pseudo-randomised trial design and matched one woman with a RRM to one woman without a RRM on year of birth, gene, and country. We estimated the hazard ratio (HR) and 95% confidence intervals (CI) for dying of breast cancer in the follow-up period. RESULTS: There were 1654 women included; 827 assigned to the RRM arm and 827 assigned to the control arm. After a mean follow-up of 6.3 years, there were 20 incident breast cancers (including 15 occult cancers) and two breast cancer deaths in the RRM arm, and 100 incident breast cancers and 7 breast cancer deaths in the control arm (HR = 0.26; 95% CI 0.05-1.35; p = 0.11). The probability of dying of breast cancer within 15 years after RRM was 0.95%. CONCLUSIONS: In women with a BRCA1 or BRCA2 pathogenic variant, RRM reduces the risk of breast cancer, and the probability of dying of breast cancer is low.

Tumor microenvironment and immune system preservation in early-stage breast cancer: routes for early recurrence after mastectomy and treatment for lobular and ductal forms of disease.

BACKGROUND: Intra-ductal cancer (IDC) is the most common type of breast cancer, with intra-lobular cancer (ILC) coming in second. Surgery is the primary treatment for early stage breast cancer. There are now irrefutable data demonstrating that the immune context of breast tumors can influence growth and metastasis. Adjuvant chemotherapy may be administered in patients who are at a high risk of recurrence. Our goal was to identify the processes underlying both types of early local recurrences. METHODS: This was a case-control observational study. Within 2 years of receiving adjuvant taxan and anthracycline-based chemotherapy, as well as modified radical mastectomy (MRM), early stage IDC and ILC recurred. Vimentin, α-smooth muscle actin (SMA), platelet-derived growth factor (PDGF), matrix metalloproteinase (MMP1), and clustered differentiation (CD95) were investigated. RESULTS: Of the samples in the ductal type group, 25 showed local recurrence, and 25 did not. Six individuals in the lobular-type group did not experience recurrence, whereas seven did. Vimentin (p = 0.000 and 0.021), PDGF (p = 0.000 and 0.002), and CD95 (p = 0.000 and 0.045) expressions were significantly different in ductal and lobular carcinoma types, respectively. Measurement of ductal type was the sole significant difference found in MMP1 (p = 0.000) and α-SMA (p = 0.000). α-SMA and CD95 were two variables that helped the recurrence mechanism in the ductal type according to the pathway analysis. In contrast, the CD95 route is a recurrent mechanism for the lobular form. CONCLUSIONS: While the immune system plays a larger role in ILC, the tumor microenvironment and immune system both influence the recurrence of IDC. According to this study, improving the immune system may be a viable cancer treatment option.

Variability in Medicaid Coverage for Gender-affirming Surgeries Across U.S. States.

OBJECTIVE: To describe the current Medicaid coverage landscape for gender-affirming surgery across the United States at the procedure level and identify factors associated with coverage. BACKGROUND: Medicaid coverage for gender-affirming surgery differs by state, despite a federal ban on gender identity-based discrimination in health insurance. States that cover gender-affirming surgery also differ in which procedures are included in Medicaid coverage, leading to confusion among patients and clinicians. METHODS: State Medicaid policies in 2021 for gender-affirming surgery were queried for each of the 50 states and the District of Columbia (D.C.). State partisanship, state-level Medicaid protections, and coverage of gender-affirming procedures in 2021 were recorded. The linear correlation between electorate partisanship and total procedures covered was assessed. Pairwise t tests were used to compare coverage based on state partisanship and the presence or absence of state-level Medicaid protections. RESULTS: Medicaid coverage for gender-affirming surgery was covered in 30 states and Washington, D.C. The most commonly covered procedures were genital surgeries and mastectomy (n = 31), followed by breast augmentation (n = 21), facial feminization (n = 12), and voice modification surgery (n = 4). More procedures were covered in Democrat-controlled or leaning states, as well as in states with explicit protections for gender-affirming care in Medicaid coverage. CONCLUSIONS: Medicaid coverage for gender-affirming surgery is patchwork across the United States and is especially poor for facial and voice surgeries. Our study provides a convenient reference for patients and surgeons detailing which gender-affirming surgical procedures are covered by Medicaid within each state.

Robotic Versus Conventional or Endoscopic-assisted Nipple-sparing Mastectomy and Immediate Prosthesis Breast Reconstruction in the Management of Breast Cancer: A Prospectively Designed Multicenter Trial Comparing Clinical Outcomes, Medical Cost, and Patient-reported Outcomes (RCENSM-P).

OBJECTIVE: To compare the clinical and patient-reported outcomes of minimal access and conventional nipple-sparing mastectomy (C-NSM). The secondary outcomes investigated included medical costs and oncological safety. BACKGROUND: Minimal-access NSM has been increasingly applied in the treatment of patients with breast cancer. However, prospective multicenter trials comparing robotic-assisted NSM (R-NSM) versus C-NSM or endoscopic-assisted NSM (E-NSM) are lacking. METHODS: A prospectively designed 3-arm multicenter, nonrandomized trial (NCT04037852) was conducted from October 1, 2019 to December 31, 2021, to compare R-NSM with C-NSM or E-NSM. RESULTS: A total of 73 R-NSM, 74 C-NSM, and 84 E-NSM procedures were enrolled. The median wound length and operation time of C-NSM was (9 cm, 175 minutes), (4 cm, and 195 minutes) in R-NSM, and (4 cm and 222 minutes) in E-NSM. Complications were comparable among the groups. Better wound healing was observed in the minimal-access NSM group. The R-NSM procedure was 4000 and 2600 United States Dollars more expensive than C-NSM and E-NSM, respectively. Wound/scar and postoperative acute pain evaluation favored the use of minimal access NSM over C-NSM. Quality of life in terms of chronic breast/chest pain, mobility, and range of motion of the upper extremity showed no significant differences. The preliminary oncologic results showed no differences among the 3 groups. CONCLUSIONS: R-NSM or E-NSM is a safe alternative if compared with C-NSM in terms of perioperative morbidities, especially with better wound healing. The advantage of minimal access groups was higher wound-related satisfaction. Higher costs remain one of the major limiting factors in the widespread adoption of R-NSM.

Association of Medicaid Expansion with Reduction in Racial Disparities in the Timely Delivery of Upfront Surgical Care for Patients With Early-Stage Breast Cancer.

OBJECTIVE: We evaluated the association between Medicaid expansion and time to surgery among patients with early-stage breast cancer (BC). BACKGROUND: Delays in surgery are associated with adverse outcomes. It is known that underrepresented minorities are more likely to experience treatment delays. Understanding the impact of Medicaid expansion on reducing racial and ethnic disparities in health care delivery is critical. METHODS: This was a population-based study including women ages 40 to 64 with stage I-II BC who underwent upfront surgery identified in the National Cancer Database (2010-2017) residing in states that expanded Medicaid on January 1, 2014. Difference-in-difference analysis compared rates of delayed surgery (>90 d from pathological diagnosis) according to time period (preexpansion [2010-2013] and postexpansion [2014-2017]) and race/ethnicity (White vs. racial and ethnic minority), stratified by insurance type (private vs. Medicaid/uninsured). Secondary analyses included logistic and Cox proportional hazards (PH) regression. All analyses were conducted among a cohort of patients in the nonexpansion states as a falsification analysis. Finally, a triple-differences approach compared preexpansion with the postexpansion trend between expansion and nonexpansion states. RESULTS: Among Medicaid expansion states, 104,569 patients were included (50,048 preexpansion and 54,521 postexpansion). In the Medicaid/uninsured subgroup, Medicaid expansion was associated with a -1.8% point (95% CI: -3.5% to -0.1, P =0.04) reduction of racial disparity in delayed surgery. Cox regression models demonstrated similar findings (adjusted difference-in-difference hazard ratio 1.12 [95% CI: 1.05 to 1.21]). The falsification analysis showed a significant racial disparity reduction among expansion states but not among nonexpansion states, resulting in a triple-difference estimate of -2.5% points (95% CI: -4.9% to -0.1%, P =0.04) in this subgroup. CONCLUSIONS: As continued efforts are being made to increase access to health care, our study demonstrates a positive association between Medicaid expansion and a reduction in the delivery of upfront surgical care, reducing racial disparities among patients with early-stage BC.

Impact of Primary Breast Surgery on Overall Survival of Patients With De Novo Metastatic Breast Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Breast surgery in cases of de novo metastatic breast cancer (MBC) is associated with improved outcomes in retrospective studies, although the results of randomized controlled trials (RCTs) are conflicting. We aimed to investigate whether surgery in this context prolongs patient survival. METHODS: We performed a systematic review of the literature to identify RCTs comparing surgery of primary breast cancer to no surgery in patients with de novo MBC. Cochrane Library, Embase, Medline (OVID), and Web of Science were searched with latest update in July 2023, while conference proceedings were manually searched. Data concerning patient and tumor characteristics, as well as outcomes, were extracted. A meta-analysis with random effects models was performed considering heterogeneity between trials. RESULTS: Overall, 3255 entries were identified and 5 RCTs fulfilled all inclusion criteria, which had enrolled 1381 patients. The overall estimation in the intention-to-treat population showed no benefit for patients who had surgical excision of the primary breast tumor (HR = 0.93; 95% CI, 0.76-1.14). No subgroups in terms of receptor status or patterns of metastasis seemed to benefit from surgery, except for younger/premenopausal patients (HR = 0.74, 95% CI, 0.58-0.94). Breast surgery was associated with improved local progression-free survival (HR = 0.37, 95% CI, 0.19-0.74). CONCLUSION: Surgery of the primary tumor in patients with de novo MBC does not prolong survival, except possibly in younger/premenopausal patients. Breast surgery should be offered within the context of well-designed clinical trials examining the issue.

A Phase II Study of Neoadjuvant PLD/Cyclophosphamide and Sequential nab-Paclitaxel Plus Dual HER2 Blockade in HER2-Positive Breast Cancer.

BACKGROUND: Neoadjuvant trastuzumab/pertuzumab (HP) plus chemotherapy for HER2-positive breast cancer (BC) achieved promising efficacy. The additional cardiotoxicity still existed. Brecan study evaluated the efficacy and safety of neoadjuvant pegylated liposomal doxorubicin (PLD)/cyclophosphamide and sequential nab-paclitaxel based on HP (PLD/C/HP-nabP/HP). PATIENTS AND METHODS: Brecan was a single-arm phase II study. Eligible patients with stages IIA-IIIC HER2-positive BC received 4 cycles of PLD, cyclophosphamide, and HP, followed by 4 cycles of nab-paclitaxel and HP. Definitive surgery was scheduled after 21 days for patients completing treatment or experiencing intolerable toxicity. The primary endpoint was the pathological complete response (pCR). RESULTS: Between January 2020 and December 2021, 96 patients were enrolled. Ninety-five (99.0%) patients received 8 cycles of neoadjuvant therapy and all underwent surgery with 45 (46.9%) breast-conserving surgery and 51 (53.1%) mastectomy. The pCR was 80.2% (95%CI, 71.2%-87.0%). Four (4.2%) experienced left ventricular insufficiency with an absolute decline in LVEF (43%-49%). No congestive heart failure and ≥grade 3 cardiac toxicity occurred. The objective response rate was 85.4% (95%CI, 77.0%-91.1%), including 57 (59.4%) complete responses and 25 (26.0%) partial responses. The disease control rate was 99.0% (95%CI, 94.3%-99.8%). For overall safety, ≥grade 3 AEs occurred in 30 (31.3%) and mainly included neutropenia (30.2%) and asthenia (8.3%). No treatment-related deaths occurred. Notably, age of >30 (P = .01; OR = 5.086; 95%CI, 1.44-17.965) and HER2 IHC 3+ (P = .02; OR = 4.398; 95%CI, 1.286-15.002) were independent predictors for superior pCR (ClinicalTrials.gov Identifier NCT05346107). CONCLUSION: Brecan study demonstrated the encouraging safety and efficacy of neoadjuvant PLD/C/HP-nabP/HP, suggesting a potential therapeutic option in HER2-positive BC.

Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer.

BACKGROUND: Poly(adenosine diphosphate-ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduce recurrence in patients with BRCA1 or BRCA2 germline mutation-associated early breast cancer. METHODS: We conducted a phase 3, double-blind, randomized trial involving patients with human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with BRCA1 or BRCA2 germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors who had received local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomly assigned (in a 1:1 ratio) to 1 year of oral olaparib or placebo. The primary end point was invasive disease-free survival. RESULTS: A total of 1836 patients underwent randomization. At a prespecified event-driven interim analysis with a median follow-up of 2.5 years, the 3-year invasive disease-free survival was 85.9% in the olaparib group and 77.1% in the placebo group (difference, 8.8 percentage points; 95% confidence interval [CI], 4.5 to 13.0; hazard ratio for invasive disease or death, 0.58; 99.5% CI, 0.41 to 0.82; P<0.001). The 3-year distant disease-free survival was 87.5% in the olaparib group and 80.4% in the placebo group (difference, 7.1 percentage points; 95% CI, 3.0 to 11.1; hazard ratio for distant disease or death, 0.57; 99.5% CI, 0.39 to 0.83; P<0.001). Olaparib was associated with fewer deaths than placebo (59 and 86, respectively) (hazard ratio, 0.68; 99% CI, 0.44 to 1.05; P = 0.02); however, the between-group difference was not significant at an interim-analysis boundary of a P value of less than 0.01. Safety data were consistent with known side effects of olaparib, with no excess serious adverse events or adverse events of special interest. CONCLUSIONS: Among patients with high-risk, HER2-negative early breast cancer and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants, adjuvant olaparib after completion of local treatment and neoadjuvant or adjuvant chemotherapy was associated with significantly longer survival free of invasive or distant disease than was placebo. Olaparib had limited effects on global patient-reported quality of life. (Funded by the National Cancer Institute and AstraZeneca; OlympiA ClinicalTrials.gov number, NCT02032823.).

Ten-year trend analysis of breast cancer, oncoplastic, and reconstructive breast surgery in a single institution (2010-2019), what has not changed?

PURPOSE: There has been a UK national directive to ensure that patients are offered reconstructive surgical options. We aimed to assess any change in oncoplastic practice over a 10-year period. METHODS: The surgical management of 7019 breast cancers was retrospectively assessed at Nightingale Breast Centre, Manchester University UK, from 2010 to 2019. The procedures were categorised into breast conservative surgery (BCS) and mastectomy ± immediate reconstruction. The data were analysed using inclusion and exclusion criteria. RESULTS: The overall rates of BCS and mastectomy were 60.1% and 39.9% respectively. No statistically significant change in the overall rates of BCS or mastectomy was observed over the last decade (p = 0.08). The rate of simple wide local excision (WLE) decreased from 98.7% to 89.3% (p < 0.001), whilst the rate of therapeutic mammoplasty (TM) increased from 1.3% to 8% (p < 0.01). The rate of chest wall perforator flaps (CWPF) changed from zero to account for 2.7% of all BCS by 2019. The overall rate of immediate breast reconstruction (IBR) did not significantly change over the study period, but it consistently remained above the national average of 27%. The rate of implant-based IBR increased from 61.3% to 76.5% (p = 0.012), whilst the rate of Latissimus Dorsi (LD) reconstruction decreased from 26.7% to 5.1% (p < 0.05). Additionally, the rate of nipple-sparing mastectomy significantly increased from 5.2% to 24%. CONCLUSION: No significant changes in the overall rates of BCS was observed, the rates of advanced breast conservation techniques, nipple-sparing mastectomy, and implant-based IBR all have increased, whilst the use of LD reconstruction decreased.

Current use of drains and management of seroma following mastectomy and axillary surgery: results of a United Kingdom national practice survey.

PURPOSE: Up to 40% of the 56,000 women diagnosed with breast cancer each year in the UK undergo mastectomy. Seroma formation following surgery is common, may delay wound healing, and be uncomfortable or delay the start of adjuvant treatment. Multiple strategies to reduce seroma formation include surgical drains, flap fixation and external compression exist but evidence to support best practice is lacking. We aimed to survey UK breast surgeons to determine current practice to inform the feasibility of undertaking a future trial. METHODS: An online survey was developed and circulated to UK breast surgeons via professional and trainee associations and social media to explore current attitudes to drain use and management of post-operative seroma. Simple descriptive statistics were used to summarise the results. RESULTS: The majority of surgeons (82/97, 85%) reported using drains either routinely (38, 39%) or in certain circumstances (44, 45%). Other methods for reducing seroma such as flap fixation were less commonly used. Wide variation was reported in the assessment and management of post-operative seromas. Over half (47/91, 52%) of respondents felt there was some uncertainty about drain use after mastectomy and axillary surgery and two-thirds (59/91, 65%) felt that a trial evaluating the use of drains vs no drains after simple breast cancer surgery was needed. CONCLUSIONS: There is a need for a large-scale UK-based RCT to determine if, when and in whom drains are necessary following mastectomy and axillary surgery. This work will inform the design and conduct of a future trial.

Information needs in breast reconstruction after mastectomy: a qualitative analysis of free-text responses from 2077 women.

BACKGROUND: For many, breast reconstruction following mastectomy (BR) forms an integral part of breast cancer survivorship. For those considering BR, provision of information is essential to allow informed decisions. Using free-text responses from a survey of breast cancer survivors, this study aims to understand current gaps in information regarding BR. METHOD: At the end of an online survey assessing BR experiences, participants were asked the open-ended question: "Thinking about women who may experience BR in the future, is there anything you think needs to change so that they have a better experience?". Responses were analysed to identify common themes. RESULTS: 3384 people completed the survey with 2,077 (61%) responding to the open-ended question. Three themes were identified: (1) content of information, (2) managing expectations, and (3) information sources, each associated with multiple subthemes. Information wanted in theme (1) covered a range of topics including BR options, risks, recovery and 'going flat.' Information on BR's psychological impact was also needed, with comments indicating many were not prepared for this. Theme (2) stressed the importance of realistic information about BR outcomes and processes to reduce discrepancies between expectations and experiences. In theme (3), peer insights and photos were important sources of realistic information. CONCLUSION: Multiple gaps exist in BR-related information available to women. BR information needs to be comprehensive, realistic, and provided at the right time to allow informed decision-making. Developing strategies to strengthen existing information provision as well as new resources to fill information gaps might enhance BR experiences.

Indocyanine green angiography guidance for vascular preservation in skin and nipple sparing mastectomy.

PURPOSE: The skin and/or nipple-sparing approach has become an oncologically sound and desirable choice for women choosing mastectomy. Indocyanine green (ICG) perfusion imaging has been shown to reduce ischemic complications in mastectomy skin flaps. Immediate reconstruction requires a well-vascularized skin flap capable of tolerating full expansion. Identification of the perforating subcutaneous vessels to the skin envelope may allow for better and more consistent blood vessel preservation and flap perfusion. METHODS: The authors conducted an institutional review board-approved prospective study with 41 patients to assess the feasibility of using ICG perfusion imaging to visualize, cutaneously map, and preserve the vessels that supply the skin flap and nipple-areolar complex. For each patient, the number of vessels initially mapped, the number of vessels preserved, the extent to which each vessel was preserved, and the proportion of the flap with adequate perfusion (as defined by the SPY-Q > 20% threshold) was recorded and analyzed. RESULTS: Vessels were able to be identified and marked in a high majority of patients (90%). There was a moderate linear relationship between the number of vessels marked and the number preserved. Successful mapping of vessels was associated with lower rates of wound breakdown (p = 0.036). Mapping and preserving at least one vessel led to excellent flap perfusion (> 90%). No increase in complications was observed from utilizing ICG angiography preoperatively. CONCLUSION: This prospective study using preoperative ICG perfusion mapping demonstrated safety, feasibility, and good prognostic outcomes. LEVEL OF EVIDENCE: III.

Global prevalence and factors associated with preoperative depression in women undergoing breast surgery: a meta-analysis and meta-regression.

PURPOSE: Depression is one of the main psychological responses experienced by patients with breast cancer perioperatively. Therefore, this review aimed to synthesize the prevalence rate of depression preoperatively among patients with breast cancer. METHODS: Six databases were searched for published articles, which recruited female patients aged 18 years and above, diagnosed with breast cancer and planned for breast surgery. Grey literatures were searched from ProQuest Theses and Dissertations, Science.gov and CogPrints. Studies published in English from the inception of databases to January 2023 were considered. Two reviewers screened, extracted, and appraised the data independently. Joanna Briggs Institute data collection form was used for data collection. Hoy's Risk of Bias Tool was utilized to assess the individual study's quality. Review Manager 5.4 software was utilized for meta-analysis. Subgroup analyses were conducted to explore the reasons for any heterogeneity. Publication bias was evaluated by Egger's test and funnel plot. RESULTS: Twenty studies involving 32,143 patients with breast cancer were included. Meta-analyses revealed an overall preoperative prevalence of 30% among all studies. Subgroup analyses showed that studies conducted in the Middle East and North Africa used purposive sampling, with patients undergoing mastectomy and lumpectomy and with moderate risk of bias reported higher prevalence of preoperative depression (54%, 44%, 40%, and 49%, respectively) as compared to other respective subgroups. CONCLUSION: The high prevalence of preoperative depression among women with breast cancer indicated the need for health care professionals to provide more psychological support to them.

Racial/ethnic disparities in the association between patient care experiences and receipt of initial surgical breast cancer care: findings from SEER-CAHPS.

PURPOSE: We determined whether racial/ethnic differences in patient experiences with care influence timeliness and type of initial surgical breast cancer treatment for a sample of female Medicare cancer patients. METHODS: We conducted a retrospective cohort study using the linked Epidemiology and End Results-Consumer Assessment of Healthcare Providers and Systems (SEER-CAHPS) dataset. The outcomes were: (1) time-to-initial surgical treatment, and (2) type of treatment [breast conserving surgery (BCS) vs. mastectomy]. The indicators were reports of four types of patient experiences with care including doctor communication, getting care quickly, getting needed care, and getting needed Rx. Interaction terms in each multivariable logistic model examined if the associations varied by race/ethnicity. RESULTS: Of the 2069 patients, 84.6% were White, 7.6% Black and 7.8% Hispanic. After adjusting for potential confounders, non-Hispanic Black patients who provided excellent reports of their ability to get needed prescriptions had lower odds of receiving surgery within 2-months of diagnosis, compared to NH-Whites who provided less than excellent reports (aOR: 0.29, 95% CI 0.09-0.98). There were no differences based on 1-month or 3-month thresholds. We found no other statistically significant effect of race/ethnicity. As to type of surgery, among NH Blacks, excellent reports of getting care quickly were associated with higher odds of receiving BCS versus mastectomy (aOR: 2.82, 95% CI 1.16-6.85) compared to NH Whites with less than excellent reports. We found no other statistically significant differences by race/ethnicity. CONCLUSION: Experiences with care are measurable and modifiable factors that can be used to assess and improve aspects of patient-centered care. Improvements in patient care experiences of older adults with cancer, particularly among minorities, may help to eliminate racial/ethnic disparities in timeliness and type of surgical treatment.

Rates of price disclosure associated with the surgical treatment of early-stage breast cancer one year after implementation of federal regulations.

PURPOSE: Mastectomy, breast reconstruction (BR) and breast conserving therapy (BCT) are core components of the treatment paradigm for early-stage disease but are differentially associated with significant financial burdens. Given recent price transparency regulations, we sought to characterize rates of disclosure for breast cancer-related surgery, including mastectomy, BCT, and BR (oncoplastic reconstruction, implant, pedicled flap and free flap) and identify associated factors. METHODS: For this cross-sectional analysis, cost reports were obtained from the Turquoise Health price transparency platform for all U.S. hospitals meeting national accreditation standards for breast cancer care. The Healthcare Cost Report Information System was used to collect facility-specific data. Addresses were geocoded to identify hospital referral and census regions while data from CMS was also used to identify the geographic practice cost index. We leveraged a Poisson regression model and relevant Medicare billing codes to analyze factors associated with price disclosure and the availability of an OOP price estimator. RESULTS: Of 447 identified hospitals, 221 (49.4%) disclosed prices for mastectomy and 188 42.1%) disclosed prices for both mastectomy and some form of reconstruction including oncoplastic reduction (n = 184, 97.9%), implants (n = 187, 99.5%), pedicled flaps (n = 89, 47.3%), and free flaps (n = 81, 43.1%). Non-profit status and increased market competition were associated with price nondisclosure. 121 hospitals (27.1%) had an out-of-pocket price estimator that included at least one breast surgery. CONCLUSIONS: Most eligible hospitals did not disclose prices for breast cancer surgery. Distinct hospital characteristics were associated with price disclosure. Breast cancer patients face persistent difficulty in accessing costs.