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.

Adherence to hormonal therapy after surgery among older women with ductal carcinoma in situ: Implications for breast cancer-related adverse health events.

BACKGROUND: Evidence from randomized clinical trials (RCTs) shows that receipt of hormonal therapy after surgery for estrogen receptor-positive ductal carcinoma in situ (DCIS) reduces the risk of DCIS and contralateral invasive breast cancer (IBC) but not death from breast cancer. RCTs examined homogeneous samples, and therefore whether this evidence can be generalized to diverse populations is unclear. METHODS: Population-based data from four state cancer registries (California, New Jersey, New York, and Texas) were analyzed on women aged 65 years and older newly diagnosed with DCIS who underwent surgery with or without radiation during the years 2006-2013. Registry records were merged with Medicare enrollment in Parts A and/or B and D (prescription drugs) and associated claims. Whether adherence to hormonal therapy was associated with adverse breast cancer-related health events was analyzed. RESULTS: Achieving excellent adherence did not affect death from breast cancer. In contrast, the risk of developing a subsequent breast tumor was 6.24 percentage points (breast-conserving surgery [BCS] with radiation therapy [RT]) and 10.54 percentage points (BCS alone) lower for women with excellent versus low adherence (p < .00001). For excellent versus good adherence, the reduced risk among women who had BCS with and without RT was approximately 3 and 5 percentage points, respectively. A similar pattern emerged for the risk of IBC among women who achieved excellent versus good or low adherence, whereas good versus low adherence comparisons were not significant. CONCLUSIONS: This analysis of a diverse population-based cohort of women with DCIS demonstrates that achieving excellent adherence to hormonal therapy is critical to minimizing the occurrence of developing subsequent breast tumors. PLAIN LANGUAGE SUMMARY: Our analysis of a diverse population-based cohort of women with ductal carcinoma in situ demonstrates that achieving excellent adherence to hormonal therapy is critical to minimizing the occurrence of developing subsequent breast tumors.

Invasive recurrence after breast conserving treatment of ductal carcinoma in situ of the breast in the Netherlands: time trends and the association with tumour grade.

BACKGROUND: The first aim of this study was to examine trends in the risk of ipsilateral invasive breast cancer (iIBC) after breast-conserving surgery (BCS) of ductal carcinoma in situ (DCIS). A second aim was to analyse the association between DCIS grade and the risk of iIBC following BCS. PATIENTS AND METHODS: In this population-based, retrospective cohort study, the Netherlands Cancer Registry collected information on 25,719 women with DCIS diagnosed in the period 1989-2021 who underwent BCS. Of these 19,034 received adjuvant radiotherapy (RT). Kaplan-Meier analyses and Cox regression models were used. RESULTS: A total of 1135 patients experienced iIBC. Ten-year cumulative incidence rates of iIBC for patients diagnosed in the periods 1989-1998, 1999-2008 and 2009-2021 undergoing BCS without RT, were 12.6%, 9.0% and 5.0% (P < 0.001), respectively. For those undergoing BCS with RT these figures were 5.7%, 3.7% and 2.2%, respectively (P < 0.001). In the multivariable analyses, DCIS grade was not associated with the risk of iIBC. CONCLUSION: Since 1989 the risk of iIBC has decreased substantially and has become even lower than the risk of invasive contralateral breast cancer. No significant association of DCIS grade with iIBC was found, stressing the need for more powerful prognostic factors to guide the treatment of DCIS.

Superparamagnetic iron oxide (SPIO) for axillary mapping in patients with ductal carcinoma in situ undergoing mastectomy: single-institution experience.

PURPOSE: Unnecessary axillary surgery can potentially be avoided in patients with DCIS undergoing mastectomy. Current guidelines recommend upfront sentinel lymph node biopsy during the index operation due to the potential of upstaging to invasive cancer. This study reviews a single institution's experience with de-escalating axillary surgery using superparamagnetic iron oxide dye for axillary mapping in patients undergoing mastectomy for DCIS. METHODS: This is a retrospective single-institution cross-sectional study. All medical records of patients who underwent mastectomy for a diagnosis of DCIS from August 2021 to January 2023 were reviewed and patients who had SPIO injected at the time of the index mastectomy were included in the study. Descriptive statistics of demographics, clinical information, pathology results, and interval sentinel lymph node biopsy were performed. RESULTS: A total of 41 participants underwent 45 mastectomies for DCIS. The median age of the participants was 58 years (IQR = 17; range 25 to 76 years), and the majority of participants were female (97.8%). The most common indication for mastectomy was diffuse extent of disease (31.7%). On final pathology, 75.6% (34/45) of mastectomy specimens had DCIS without any type of invasion and 15.6% (7/45) had invasive cancer. Of the 7 cases with upgrade to invasive disease, 2 (28.6%) of them underwent interval sentinel lymph node biopsy. All sentinel lymph nodes biopsied were negative for cancer. CONCLUSION: The use of superparamagnetic iron oxide dye can prevent unnecessary axillary surgery in patients with DCIS undergoing mastectomy.

Nationwide Analysis of Locoregional Management for Ductal Carcinoma In Situ in Males: An NCDB Analysis of the Surgical Approach to DCIS in Males.

BACKGROUND: Limited data exist regarding the optimal locoregional approach for males with ductal carcinoma in situ (DCIS). This study examined trends in management and survival for males with DCIS. METHODS: The National Cancer Database (NCDB) was queried for males with a diagnosis of DCIS from 2006 to 2017. Patients were categorized by locoregional management. Continuous variables were evaluated by Kruskal-Wallis and categorical variables by chi-square or Fisher's exact test. Univariable and multivariable logistic regressions were performed to evaluate for predictors of patients receiving partial mastectomy (PM) with radiation. Survival was analyzed by Kaplan-Meier. RESULTS: Between 2006 and 2017, 711 males with DCIS were identified. Most received mastectomy alone (57.1%). No change was observed in management approach from 2006 to 2017. Patients who underwent mastectomy alone were mostly hormone-positive (95.9% were estrogen-positive, 90.9% were progesterone-positive), although this cohort was least likely to receive hormone therapy (17.2%). Among those who underwent PM with radiation, only 61% of those who were hormone-positive received hormone therapy. Univariable analysis demonstrated that those of black race had lower odds of receiving PM with radiation (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.36-0.84), which persisted in the multivariable analysis with control for age and tumor size (OR, 0.32; 95% CI, 0.15-0.67). Overall survival did not differ significantly between the four treatment methods (p = 0.08). CONCLUSIONS: The management approach to male DCIS did not change from 2006 to 2017. Survival did not differ between treatment methods. Demographic and clinicopathologic features, including race, may influence locoregional treatments received, and further studies are needed to further understand this.

Intraoperative Radiation Therapy for Early-Stage Breast Cancer: Updated Outcomes from a Single-Institution Experience.

BACKGROUND: Increasingly, data have supported the use of partial-breast irradiation (PBI) for low-risk patients after breast-conserving surgery, with techniques allowing for completion of treatment in 1-3 weeks. Intraoperative radiation therapy (IORT) is an alternative to PBI. Our institution had used low-energy photon IORT (TARGIT) for more than a decade. The initial results demonstrated a 2% local recurrence rate with a short follow-up period of 2 years. This report presents updated outcomes during with 5-year follow-up. METHODS: A review of an institutional review board (IRB)-approved institutional registry was performed. The review identified 215 patients with early-stage breast cancer (stages 0-IIA) who received IORT. At the time of surgery, IORT was delivered with 20 Gy in a single fraction, with 5.1% (n = 11) of patients receiving additional whole-breast irradiation (WBI). RESULTS: The mean age at diagnosis was 71 years (range, 49-98 years), and the median follow-up was 5.7 years (interquartile range [IQR], 4.2-7.0 years). Of the 215 patients, 2.8% (n = 6) had ductal carcinoma in situ (DCIS), 90.7% (n = 195) had T1 disease, and 6.5% (n = 14) had T2 disease. Endocrine therapy was prescribed for 79% and chemotherapy for 1.4% of the patients. The 5-year rates were 5.3% for local recurrence, 6.4% for locoregional recurrence, and 2.7% for distant metastases. At 5 years, 93% of the patients were alive. CONCLUSIONS: The 5-year outcomes with TARGIT IORT demonstrated high rates of local recurrence, exceeding those seen with alternative modern approaches. The local recurrence outcomes with IORT are more consistent with studies omitting radiation following breast-conserving surgery, using endocrine therapy alone. Consistent with current guidelines and previous data, TARGIT IORT should not be used as monotherapy outside prospective clinical trials.

Clinicopathological Predictors of Positive Resection Margins in Breast-Conserving Surgery.

BACKGROUND: Ductal carcinoma in situ (DCIS) is associated with risk of positive resection margins following breast-conserving surgery (BCS) and subsequent reoperation. Prior reports grossly underestimate the risk of margin positivity with IBC containing a DCIS component (IBC + DCIS) due to patient-level rather than margin-level analysis. OBJECTIVE: The aim of this study was to delineate the relative risk of IBC + DCIS compared with pure IBC (without a DCIS component) on margin positivity through detailed margin-level interrogation. METHODS: A single institution, retrospective, observational cohort study was conducted in which pathology databases were evaluated to identify patients who underwent BCS over 5 years (2014-2019). Margin-level interrogation included granular detail into the extent, pathological subtype and grade of disease at each resection margin. Predictors of a positive margin were computed using multivariate regression analysis. RESULTS: Clinicopathological details were examined from 5454 margins from 909 women. The relative risk of a positive margin with IBC + DCIS versus pure IBC was 8.76 (95% confidence interval [CI] 6.64-11.56) applying UK Association of Breast Surgery guidelines, and 8.44 (95% CI 6.57-10.84) applying the Society of Surgical Oncology/American Society for Radiation Oncology guidelines. Independent predictors of margin positivity included younger patient age (0.033, 95% CI 0.006-0.060), lower specimen weight (0.045, 95% CI 0.020-0.069), multifocality (0.256, 95% CI 0.137-0.376), lymphovascular invasion (0.138, 95% CI 0.068-0.208) and comedonecrosis (0.113, 95% CI 0.040-0.185). CONCLUSIONS: Compared with pure IBC, the relative risk of a positive margin with IBC + DCIS is approximately ninefold, significantly higher than prior estimates. This margin-level methodology is believed to represent the impact of DCIS more accurately on margin positivity in IBC.

Is the Number or Proximity of Margins Less than 2 mm Associated with an Increased Mastectomy Rate in Patients Attempting Breast Conservation Therapy for Ductal Carcinoma In Situ?

BACKGROUND: Consensus guidelines recommend ≥ 2 mm margins in patients undergoing partial mastectomy (PM) for ductal carcinoma in situ (DCIS). It is unknown whether the number or proximity of margins less than 2 mm is associated with an increased mastectomy rate in patients attempting breast conservation therapy (BCT) for DCIS. The aim of this study is to examine this relationship. PATIENTS AND METHODS: An institutional database review identified 208 patients with DCIS who underwent PM at a tertiary referral center and community hospitals from July 2020 to June 2023. Patients with a history of breast cancer, previous surgery for breast cancer, ipsilateral invasive carcinoma, papillary carcinoma, Paget's disease, more lobular carcinoma in situ (LCIS) than DCIS present, initial mastectomy, no DCIS present, routine shave margins (of all vectors), and ≥ 2 mm margins of all six vectors were excluded. Selective intraoperative margin re-excisions were included. RESULTS: A total of 208 patients who met inclusion criteria were retrospectively reviewed. 122 (25%) had one close/positive (< 2 mm) margin and 86 (18%) had two or more close/positive margins. Of the patients with one close/positive margin, 7% (9/122) eventually underwent mastectomy. Of the patients with two or more close/positive margins, 20% (17/86) eventually underwent mastectomy. Overall, no patients with opposing margins underwent mastectomy. CONCLUSIONS: Patients undergoing PM for DCIS have a mastectomy rate that is increased threefold, with two or more close/positive margins at initial PM, when compared with those with only one close/positive margin. The presence of opposing close/positive margins at initial PM did not increase the mastectomy rate and most were cleared with re-excision.

Nodal Surgery for Patients ≥ 70 Undergoing Mastectomy for DCIS? Choose Wisely.

BACKGROUND: Routine sentinel lymphadenectomy (SLNB) for early-stage HR+/HER2- breast cancer in women ≥70 is discouraged by Choosing Wisely, but whether SLNB can be routinely omitted in women ≥70 with DCIS undergoing mastectomy is unclear. This study aims to evaluate rates of axillary surgery and nodal positivity (pN+) in this population to determine the impact of axillary surgery on treatment decisions. METHODS: Females ≥70 with DCIS undergoing mastectomy were identified from the National Cancer Database (2012-2020). The rate of upstaging to invasive cancer (≥pT1) or pN+ was assessed. Subset analyses were conducted for ER+ patients. Adjuvant therapies were evaluated among ≥pT1 patients after stratifying by nodal status. RESULTS: Of 9,030 patients, 1,896 (21%) upstaged to ≥pT1. Axillary surgery was performed in 86% of patients, predominantly sentinel lymphadenectomy (SLNB, 65%). Post hoc application of Choosing Wisely criteria demonstrated that 93% of the entire cohort and 97% of ER+ DCIS patients could have avoided axillary surgery. Nodal positivity was 0.3% among those who didn't upstage, and 12% among those upstaging to ≥pT1, with <2% having pN2-3 disease, irrespective of receptor subtype. Node-positive patients had higher adjuvant therapy usage, but there was no recommendation for adjuvant chemotherapy or radiation for 71% and 66% of pN+ patients, respectively. CONCLUSIONS: Axillary surgery can be omitted for most patients ≥70 undergoing mastectomy for ER+ DCIS, aligning with recommendations for invasive cancer, and omission can be considered in those with ER- disease. Future guidelines incorporating preoperative imaging, as in the SOUND trial, may aid in identifying patients benefiting from axillary surgery.

Evaluating the Effect of MarginProbe® Use on Re-excisions After Partial Mastectomy: A Single-Institution Analysis.

BACKGROUND: Breast conservation therapy is a widely accepted approach in treating breast cancer, yet the average re-excision rates are approximately 25% despite surgical advancements. The Food and Drug Administration (FDA)-approved MarginProbe® device uses radiofrequency spectroscopy for intraoperative margin assessment, potentially reducing re-excision rates. This study evaluated the effectiveness of MarginProbe® in reducing re-excisions compared with standard of care (SOC). METHODS: A prospective cohort with MarginProbe® usage during partial mastectomies from June 2019 to July 2023 (153 patients) was compared with a retrospective control group without the device from January 2015 to May 2019 (300 patients). Both groups underwent partial mastectomies performed by two breast surgeons. Positive margins were defined as tumor on ink for invasive cancers and within 2 mm for ductal carcinoma in situ. RESULTS: When control was used for patient demographics and tumor characteristics, the findings showed that MarginProbe® significantly decreased the probability of re-excision by 58% (p < 0.001), although it led to a higher shave volume, with an average of 9.8 cc additional tissue removed compared with SOC (p < 0.001). Human epidermal growth factor 2 (HER2) positivity was significantly associated with increased odds of re-excision (p = 0.036). MarginProbe® demonstrated a sensitivity of 70.1% and a specificity of 47.5%. CONCLUSIONS: MarginProbe® is an effective adjunct for intraoperative margin assessment to decrease re-excision rates. However, patient selection is paramount. Given its significant increase in shave volume, women with small breasts may be at higher risk for poor cosmesis. Surgeons should exercise clinical judgement when determining the suitability of MarginProbe® use for patients undergoing breast conservation. Further research is necessary to refine MarginProbe®'s specificity and to optimize its clinical application.

The Clinical Utility of a 7-Gene Biosignature on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery: An Updated Analysis of the DCISionRT® PREDICT Study.

BACKGROUND: Breast-conserving surgery (BCS) followed by adjuvant radiotherapy (RT) is a standard treatment for ductal carcinoma in situ (DCIS). A low-risk patient subset that does not benefit from RT has not yet been clearly identified. The DCISionRT test provides a clinically validated decision score (DS), which is prognostic of 10-year in-breast recurrence rates (invasive and non-invasive) and is also predictive of RT benefit. This analysis presents final outcomes from the PREDICT prospective registry trial aiming to determine how often the DCISionRT test changes radiation treatment recommendations. METHODS: Overall, 2496 patients were enrolled from February 2018 to January 2022 at 63 academic and community practice sites and received DCISionRT as part of their care plan. Treating physicians reported their treatment recommendations pre- and post-test as well as the patient's preference. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendation. The impact of the test on RT treatment recommendation was physician specialty, treatment settings, individual clinical/pathological features and RTOG 9804 like criteria. Multivariate logisitc regression analysis was used to estimate the odds ratio (ORs) for factors associated with the post-test RT recommendations. RESULTS: RT recommendation changed 38% of women, resulting in a 20% decrease in the overall recommendation of RT (p < 0.001). Of those women initially recommended no RT (n = 583), 31% were recommended RT post-test. The recommendation for RT post-test increased with increasing DS, from 29% to 66% to 91% for DS <2, DS 2-4, and DS >4, respectively. On multivariable analysis, DS had the strongest influence on final RT recommendation (odds ratio 22.2, 95% confidence interval 16.3-30.7), which was eightfold greater than clinicopathologic features. Furthermore, there was an overall change in the recommendation to receive RT in 42% of those patients meeting RTOG 9804-like low-risk criteria. CONCLUSIONS: The test results provided information that changes treatment recommendations both for and against RT use in large population of women with DCIS treated in a variety of clinical settings. Overall, clinicians changed their recommendations to include or omit RT for 38% of women based on the test results. Based on published clinical validations and the results from current study, DCISionRT may aid in preventing the over- and undertreatment of clinicopathological 'low-risk' and 'high-risk' DCIS patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03448926 ( https://clinicaltrials.gov/study/NCT03448926 ).

Determination of Factors Associated with Upstage in Atypical Ductal Hyperplasia to Identify Low-Risk Patients Where Active Surveillance May be an Alternative.

BACKGROUND: Excision is routinely recommended for atypical ductal hyperplasia (ADH) found on core biopsy given cancer upstage rates of near 20%. Identifying a cohort at low-risk for upstage may avoid low-value surgery. Objectives were to elucidate factors predictive of upstage in ADH, specifically near-complete core sampling, to potentially define a group at low upstage risk. PATIENTS AND METHODS: This retrospective, cross-sectional, multi-institutional study from 2015 to 2019 of 221 ADH lesions in 216 patients who underwent excision or active observation (≥ 12 months imaging surveillance, mean follow-up 32.6 months) evaluated clinical, radiologic, pathologic, and procedural factors for association with upstage. Radiologists prospectively examined imaging for lesional size and sampling proportion. RESULTS: Upstage occurred in 37 (16.7%) lesions, 25 (67.6%) to ductal carcinoma in situ (DCIS) and 12 (32.4%) to invasive cancer. Factors independently predictive of upstage were lesion size ≥ 10 mm (OR 5.47, 95% CI 2.03-14.77, p < 0.001), pathologic suspicion for DCIS (OR 12.29, 95% CI 3.24-46.56, p < 0.001), and calcification distribution pattern (OR 8.08, 95% CI 2.04-32.00, p = 0.003, "regional"; OR 19.28, 95% CI 3.47-106.97, p < 0.001, "linear"). Near-complete sampling was not correlated with upstage (p = 0.64). All three significant predictors were absent in 65 (29.4%) cases, with a 1.5% upstage rate. CONCLUSIONS: The upstage rate among 221 ADH lesions was 16.7%, highest in lesions ≥ 10 mm, with pathologic suspicion of DCIS, and linear/regional calcifications on mammography. Conversely, 30% of the cohort exhibited all low-risk factors, with an upstage rate < 2%, suggesting that active surveillance may be permissible in lieu of surgery.

Upgrade Rates and Breast Cancer Development Among Germline Pathogenic Variant Carriers with High-Risk Breast Lesions.

BACKGROUND: High-risk lesions (HRL) of the breast are risk factors for future breast cancer development and may be associated with a concurrent underlying malignancy when identified on needle biopsy; however, there are few data evaluating HRLs in carriers of germline pathogenic variants (PVs) in breast cancer predisposition genes. METHODS: We identified patients from two institutions with germline PVs in high- and moderate-penetrance breast cancer predisposition genes and an HRL in an intact breast, including atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), and lobular neoplasia (LN). We calculated upgrade rates at surgical excision and used Kaplan-Meier methods to characterize 3-year breast cancer risk in patients without upgrade. RESULTS: Of 117 lesions in 105 patients, 65 (55.6%) were ADH, 48 (41.0%) were LN, and 4 (3.4%) were FEA. Most PVs (83.8%) were in the BRCA1/2, CHEK2 and ATM genes. ADH and FEA were excised in most cases (87.1%), with upgrade rates of 11.8% (95% confidence interval [CI] 5.5-23.4%) and 0%, respectively. LN was selectively excised (53.8%); upgrade rate in the excision group was 4.8% (95% CI 0.8-22.7%), and with 20 months of median follow-up, no same-site cancers developed in the observation group. Among those not upgraded, the 3-year risk of breast cancer development was 13.1% (95% CI 6.3-26.3%), mostly estrogen receptor-positive (ER +) disease (89.5%). CONCLUSIONS: Upgrade rates for HRLs in patients with PVs in breast cancer predisposition genes appear similar to non-carriers. HRLs may be associated with increased short-term ER+ breast cancer risk in PV carriers, warranting strong consideration of surgical or chemoprevention therapies in this population.

Lobular Neoplasia Diagnosed by MRI-Guided Breast Biopsy: Identifying Upgrade Rate to Malignancy and Outcomes of Clinical and Surgical Management.

OBJECTIVE: The aim of this study was to determine surgical and clinical outcomes of lobular neoplasia (LN) diagnosed by magnetic resonance imaging (MRI) biopsy, including upgrade to malignancy, and to assess for characteristics associated with upgrade. METHOD: A single-institution retrospective study, between 2013 and 2022, of patients with histopathological findings of LN via MRI-guided biopsy was performed using an institutional database and review of the electronic medical records. Decision for excision or surveillance was made by a multidisciplinary team per institutional practice. Patient demographics and imaging characteristics were summarized using descriptive analyses. Upgrade was defined as upgrade to cancer on surgical pathology for patients treated with excision or the development of cancer at the biopsy site during surveillance. The Wilcoxon rank-sum test and Fisher's exact test were used to compare features of the upgraded cohort with the remainder of the group. RESULTS: Ninety-four MRI biopsies diagnosing LN were included. Median age was 57 years (range 37-78 years). Forty-six lesions underwent excision while 48 lesions were surveilled. The upgrade rate was 7.4% (7/94). Upgrades in the excised cohort consisted of pleomorphic lobular carcinoma in situ (LCIS; n = 1), ductal carcinoma in situ (DCIS; n = 3) and invasive lobular carcinoma (ILC; n = 2), while one interval development of DCIS was observed at the site of biopsy in the surveillance cohort. No MRI or patient variables were associated with upgrade. CONCLUSIONS: In this contemporary cohort of MRI-detected LNs, the upgrade rate was low. Omission of surgery for MRI-detected LNs in carefully selected patients may be considered in a shared decision-making capacity between the patient and the treatment team. Larger cohorts are needed to determine factors predictive of upgrade risk.

Positive Nipple Margins in Nipple-Sparing Mastectomy: Management of Nipples Containing Cancer or Atypia.

BACKGROUND: Nipple-sparing mastectomy (NSM) is an oncologically safe approach for breast cancer treatment and prevention; however, there are little long-term data to guide management for patients whose nipple margins contain tumor or atypia. METHODS: NSM patients with tumor or atypia in their nipple margin were identified from a prospectively maintained, single-institution database of consecutive NSMs. Patient and tumor characteristics, treatment, recurrence, and survival data were assessed. RESULTS: A total of 3158 NSMs were performed from June 2007 to August 2019. Nipple margins contained tumor in 117 (3.7%) NSMs and atypia only in 164 (5.2%) NSMs. Among 117 nipple margins that contained tumor, 34 (29%) margins contained invasive cancer, 80 (68%) contained ductal carcinoma in situ only, and 3 (3%) contained lymphatic vessel invasion only. Management included nipple-only excision in 67 (57%) breasts, nipple-areola complex excision in 35 (30%) breasts, and no excision in 15 (13%) breasts. Only 23 (24%) excised nipples contained residual tumor. At 67 months median follow-up, there were 2 (1.8%) recurrences in areolar or peri-areolar skin, both in patients with nipple-only excision. Among 164 nipple margins containing only atypia, 154 (94%) nipples were retained. At 60 months median follow-up, no patient with atypia alone had a nipple or areola recurrence. CONCLUSIONS: Nipple excision is effective management for nipple margins containing tumor. No intervention is required for nipple margins containing only atypia. Our results support broad eligibility for NSM with careful nipple margin assessment.

Potential Overtreatment of DCIS in Patients with Limited Life Expectancy.

INTRODUCTION: As the benefits of intensive locoregional therapy for ductal carcinoma in situ (DCIS) are realized over time in older adults, life expectancy may help to guide treatment decisions. We examined whether life expectancy was associated with extent of locoregional therapy in this population. PATIENTS AND METHODS: Women ≥ 70 years old with < 5 cm of DCIS diagnosed 2010-2015 were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset and categorized by a life expectancy ≤ 5 or > 5 years, defined by a validated claims-based measure. Differences in locoregional therapy (mastectomy + axillary surgery, mastectomy-only, lumpectomy + radiation therapy (RT) + axillary surgery, lumpectomy + RT, lumpectomy-only, and no treatment) by life expectancy were assessed using Pearson chi-squared tests. Generalized linear mixed models were used to identify factors associated with receipt of lumpectomy-only. RESULTS: Of 5346 women (median age of 75 years, range 70-97 years), 927 (17.3%) had a life expectancy ≤ 5 years. Of the 4041 patients who underwent lumpectomy, 710 (13.3%) underwent axillary surgery. More patients with life expectancy ≤ 5 years underwent lumpectomy-only (39.4% versus 27%), mastectomy-only (8.1% versus 5.3%), or no treatment (5.8% versus 3.2%; p < 0.001). On multivariable analysis, women with life expectancy ≤ 5 years had a significantly greater likelihood of undergoing lumpectomy-only [OR 1.90, 95% CI (1.63-2.22)]. CONCLUSIONS: Life expectancy is associated with lower-intensity locoregional therapy for older women with DCIS, yet a large proportion of patients with a life expectancy ≤ 5 years received RT and axillary surgery, highlighting potential overtreatment and opportunities to de-escalate locoregional therapy in older adults.

Contrast-Enhanced Mammography in Local Staging of Screen-Detected Breast Cancer.

BACKGROUND: BreastScreen Australia, the population mammographic screening program for breast cancer, uses two-view digital screening mammography ± ultrasound followed by percutaneous biopsy to detect breast cancer. Secondary breast imaging for further local staging, not performed at BreastScreen, may identify additional clinically significant breast lesions. Staging options include further mammography, bilateral ultrasound, and/or contrast-based imaging (CBI) [magnetic resonance imaging (MRI) or contrast-enhanced mammography (CEM)]. CBI for local staging of screen-detected cancer was introduced at an academic hospital breast service in Melbourne, VIC, Australia. We report findings for otherwise occult disease and resulting treatment changes. MATERIAL AND METHODS: Patients staged using CEM between November 2018 and April 2022 were identified from hospital records. Data were extracted from radiology, pathology, and breast unit databases. CEM-detected abnormalities were documented as true positive (TP) for invasive cancer or ductal carcinoma in situ (DCIS), or otherwise false positive (FP). The impact on surgical decisions was assessed. RESULTS: Of 202 patients aged 44-84 years, 60 (30%) had 74 additional findings [34 (46%) TP, 40 (54%) FP]. These were malignant in 29/202 (14%) patients (79% invasive cancers, 21% DCIS). CEM resulted in surgical changes in 43/202 (21%) patients: wider resection (24/43), conversion to mastectomy (6/43), contralateral breast surgery (6/43), additional ipsilateral excision (5/43), and bracketing (2/43). Additional findings were more common for patients with larger index lesions and for invasive cancer, but there was no significant variation by age, breast density, or index lesion grade. CONCLUSIONS: CEM for local staging of screen-detected breast cancers identified occult malignancy in 14% of patients. CEM improves local staging and may facilitate appropriate management of screen-detected breast cancers.

Disease-specific survival outcomes for patients after locoregional treatment for ductal carcinoma in situ: observational cohort study.

BACKGROUND: Breast-conserving surgery alone, breast-conserving surgery with adjuvant radiation treatment, and mastectomy are guideline-concordant treatments for ductal carcinoma in situ. The aim of this study was to compare survival outcomes between these treatment options. METHODS: A stratified random sample of patients diagnosed with pure ductal carcinoma in situ between 2008 and 2014 was selected from 1330 sites in the USA. Data on diagnosis, treatment, and follow-up were abstracted by local cancer registrars. Population-averaged marginal estimates of disease-specific survival and overall survival for breast-conserving surgery alone, breast-conserving surgery with radiation treatment, and mastectomy were obtained by combining sampling and overlap weights. RESULTS: A total of 18 442 women were included, with a median follow-up of 67.8 (interquartile range 46.1-93.5) months. A total of 35 women died from breast cancer, at a median age of 62 (interquartile range 50-74) years. Population-averaged 8-year rates of disease-specific survival were 99.6% or higher for all treatment groups, with no significant differences between groups (breast-conserving surgery alone versus breast-conserving surgery with radiation treatment, HR 1.19 (95% c.i. 0.29 to 4.85); and mastectomy versus breast-conserving surgery with radiation treatment, HR 1.74 (95% c.i. 0.53 to 5.72). There was no difference in overall survival between the patients who underwent a mastectomy and the patients who underwent breast-conserving surgery with radiation treatment (HR 1.09 (95% c.i. 0.83 to 1.43)). Patients who underwent breast-conserving surgery alone had lower overall survival compared with the patients who underwent breast-conserving surgery with radiation treatment (HR 1.29 (95% c.i. 1.00 to 1.67)). This survival difference vanished for all but one subgroup, namely patients less than 65 years (HR 1.86 (95% c.i. 1.15 to 3.00)). CONCLUSION: There was no statistically significant difference in disease-specific survival between women operated with breast-conserving surgery alone, breast-conserving surgery with radiation treatment, or mastectomy for ductal carcinoma in situ. Given the low absolute risk of disease-specific mortality, these results provide confidence in offering individualized locoregional treatment without fear of compromising survival.

Radial sclerosing lesions found on core needle biopsy: excision can be safely avoided.

AIMS: Radial sclerosing lesions (RSLs) are benign breast lesions composed of glandular and epithelial proliferations with stellate architecture and fibro-elastotic stroma, which can mimic invasive carcinoma on imaging. Surgical management following a core biopsy diagnosis of RSLs remains controversial. METHODS AND RESULTS: We retrospectively identified core biopsies with RSLs without atypia who underwent subsequent surgical excision between 2015 and 2021. All core biopsy slides were reviewed to confirm the diagnosis. Imaging was reviewed to determine radiological-pathological concordance. An upgrade was defined as invasive carcinoma or ductal carcinoma in situ (DCIS) in the excision. The final cohort consisted of 130 core biopsies from 124 women (median age = 52 years, range = 27-76). The imaging modality was mammogram in 52 (40%) cases, MRI in 52 (40%) and ultrasound in 26 (20%). One hundred and seven (82%) core biopsies were vacuum-assisted and 23 (18%) were ultrasound-guided without vacuum assistance. The median lesion size on imaging was 9 mm (range = 2-41). Overall, two (1%) cases were upgraded at excision, including one microinvasive lobular carcinoma and one 2 mm focus of invasive mammary carcinoma with associated DCIS. In both cases, the upgraded foci of carcinoma were not closely associated with the biopsy site and were considered incidental upgrades. CONCLUSIONS: This study adds to the body of literature supporting observation, rather than routine excision of radial sclerosing lesions without atypia.

Evaluation of the Efficacy of Postoperative Adjuvant Therapy for HER2-Positive Ductal Carcinoma in Situ with Microinvasion.

A retrospective study on 90 eligible HER2+ ductal carcinoma in situ with microinvasion (DCIS-MI) patients was performed with a median follow-up time of 57 months. The baseline was consistent between the 4-cycle and 6-cycle chemotherapy groups. There were more patients with multiple foci of micrometastasis in the target therapy group in the two groups with or without target therapy (p < 0.01). Postoperative chemotherapy with a 4-cycle regimen can achieve the expected therapeutic effect in patients with HER2+ DCIS-MI, but the role of target therapy in HER2+ DCIS-MI patients has not been confirmed.