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.

Phase II Trial of Five-Fraction Accelerated Partial Breast Irradiation Using Noninvasive Image-Guided Breast Brachytherapy.

PURPOSE/OBJECTIVE(S): NIBB has potential advantages over other APBI techniques by delivering highly conformal radiation with minimal collateral dose to the heart and lung compared with external beam techniques, but unlike other brachytherapy techniques NIBB is non-invasive. Previous data has shown encouraging outcomes using a 10-fraction regimen. To improve efficiency, convenience, and cost, reduction in the fraction number is desirable. Final results of a prospective phase II trial are reported. MATERIALS/METHODS: NIBB APBI was delivered using 28.5Gy in 5 fractions daily over 1 week. Patient eligibility criteria required: invasive carcinoma ≤2.0 cm or DCIS ≤3.0 cm, ER positive (if invasive), lymph node negative, LVI absent, and lumpectomy with margins negative by 2mm. The primary endpoint was grade ≥ 2 subcutaneous fibrosis/induration <30%. Secondary endpoints included any late toxicity, cosmetic outcome, and local control. RESULTS: 40 patients were treated with a median follow-up of 59.7 months. The mean age was 67 years (50-89 years) and tumor size was 1.0cm (0.3-2.0cm). 80% had invasive carcinoma. The mean breast separation with compression was 6.7cm (3.5-8.9cm). The 5-year actuarial local control was 96.6% and overall survival was 96.9%. Grade 2 and 3 late toxicities were 15% and 0%, respectively. The rate of grade 2 subcutaneous fibrosis/induration was 2.5% (+/-2.5%) meeting the study's primary endpoint. The most common late toxicity of any grade was skin telangiectasia; 22.5% grade 1 and 15% grade 2. Only breast separation was associated with telangiectasia risk, p=0.002. Overall cosmetic outcome was excellent, good, and fair/poor in 75%, 25%, and 0%, respectively. CONCLUSIONS: NIBB APBI delivered in 5 fractions results in a low rate of late toxicity and a high rate of good/excellent cosmetic outcomes. Telangiectasia risk can be minimized by keeping breast separation ≤7.0cm. The local failure rate was appropriately low. Further investigation of this technique is warranted.

Does Preoperative MRI Reduce Positive Margins after Breast-Conserving Surgery?

BACKGROUND: Breast-conserving surgery (BCS) is a mainstay for breast cancer management, and obtaining negative margins is critical. Some have advocated for the use of preoperative magnetic resonance imaging (MRI) in reducing positive margins after BCS. We sought to determine whether preoperative MRI was associated with reduced positive margins. PATIENTS AND METHODS: The SHAVE/SHAVE2 trials were multicenter trials in ten US centers with patients with stage 0-3 breast cancer undergoing BCS. Use of preoperative MRI was at the discretion of the surgeon. We evaluated whether or not preoperative MRI was associated with margin status prior to randomization regarding resection of cavity with shave margins. RESULTS: A total of 631 patients participated. Median age was 64 (range 29-94) years, with a median tumor size of 1.3 cm (range 0.1-9.3 cm). Patient factors included 26.1% of patients (165) had palpable tumors, and 6.5% (41) received neoadjuvant chemotherapy. Tumor factors were notable for invasive lobular histology in 7.0% (44) and extensive intraductal component (EIC) in 32.8% (207). A preoperative MRI was performed in 193 (30.6%) patients. Those who underwent preoperative MRI were less likely to have a positive margin (31.1% versus 38.8%), although this difference was not statistically significant (p = 0.073). On multivariate analysis, controlling for patient and tumor factors, utilization of preoperative MRI was not a significant factor in predicting margin status (p = 0.110). Rather, age (p = 0.032) and tumor size (p = 0.040) were the only factors associated with margin status. CONCLUSION: These data suggest that preoperative MRI is not associated margin status; rather, patient age and tumor size are the associated factors.

Breast-Specific Sensuality in Breast Cancer Survivors: Sexually Active or Not.

BACKGROUND: We sought to better understand breast-specific sensuality (BSS) in sexually inactive breast cancer survivors. METHODS: We conducted an anonymous cross-sectional survey of breast cancer survivors during surveillance appointments from 2014 to 2016. Sexual inactivity was defined as no sexual activity within 4 weeks prior. Categorical data were analyzed using Fisher's exact test. Multiple logistic regression adjusted for age and menopausal status, and Firth's bias correction accommodated sparse data. RESULTS: Of 585 respondents, 546 (93.3%) were between the ages of 40 and 79 years, of whom 285 (48.7%) were sexually inactive. Favorable post-treatment appearance satisfaction was reported by 413 (71.0%) respondents. Sexually inactive respondents were more likely to score discomfort with their partner seeing their chest after surgery compared with sexually active respondents (41 [20.4%] vs. 34 [11.4%]; p = 0.002). Both sexually inactive and active respondents reported that their chest was important in intimacy after surgery but at significantly different rates (117 [44.3%] vs. 217 [72.6%]; p < 0.001). Post-surgical appearance satisfaction for sexually inactive respondents was positively associated with level of comfort with partner seeing their chest after surgery (p < 0.001) and with rating of a pleasurable caress of the treated breast (p < 0.001). CONCLUSIONS: Over 40% of sexually inactive respondents reported their chest was important in intimacy after surgery, suggesting that BSS may be a route to intimacy for sexually inactive breast cancer survivors. Post-surgical breast appearance satisfaction significantly correlated with comfort being seen by one's partner and appreciation of a pleasurable breast caress. Optimizing breast cancer surgical aesthetic outcomes may improve survivorship.

Omission of Radiation in Conservative Treatment for Breast Cancer: Opportunity for De-escalation of Care.

INTRODUCTION: De-escalation of breast cancer treatment aims to reduce patient and financial toxicity without compromising outcomes. Level I evidence and National Comprehensive Cancer Network guidelines support omission of adjuvant radiation in patients aged >70 y with hormone-sensitive, pT1N0M0 invasive breast cancer treated with endocrine therapy. We evaluated radiation use in patients eligible for guideline concordant omission of radiation. METHODS: Subgroup analysis of patients eligible for radiation omission from two pooled randomized controlled trials, which included stage 0-III breast cancer patients undergoing breast conserving surgery, was performed to evaluate factors associated with radiation use. RESULTS: Of 631 patients, 47 (7.4%) met radiation omission criteria and were treated by 14 surgeons at eight institutions. The mean age was 75.3 (standard deviation + 4.4) y. Majority of patients identified as White (n = 46; 97.9%) and non-Hispanic (n = 44; 93.6%). The mean tumor size was 1.0 cm; 37 patients (88.1%) had ductal, 4 patients (9.5%) had lobular, and 17 patients (40.5%) had low-grade disease. Among patients eligible for radiation omission, 34 (72.3%) patients received adjuvant radiation. Those who received radiation were significantly younger than those who did not (74 y, interquartile range = 4 y, versus 78 y, interquartile range = 11 y, P = 0.03). There was no difference in radiation use based on size (P = 0.4), histology (P = 0.5), grade (P = 0.7), race (P = 1), ethnicity (P = 0.6), institution (P = 0.1), gender of the surgeon (P = 0.7), or surgeon (P = 0.1). CONCLUSIONS: Fewer than 10% of patients undergoing breast conservation met criteria for radiation omission. Nearly three-quarters received radiation therapy with younger age being a driver of radiation use, suggesting ample opportunity for de-escalation, particularly among younger eligible patients.

Does Localization Technique Matter for Non-palpable Breast Cancers?

BACKGROUND: There are several techniques for localization of non-palpable breast tumors, but comparisons of these techniques in terms of margin positivity and volume of tissue resected are lacking. METHODS: Between 2011-2013 and 2016-2018, 2 randomized controlled trials involving 10 centers across the United States accrued 631 patients with stage 0-3 breast cancer, all of whom underwent breast conserving surgery. Of these, 522 had residual non-palpable tumors for which localization was required. The localization technique was left to the discretion of the individual surgeon. We compared margin positivity and volume of tissue resected between various localization techniques. RESULTS: The majority of the patients (n = 465; 89.1%) had wire localization (WL), 50 (9.6%) had radioactive seed (RS) localization, and 7 (1.3%) had Savi Scout (SS) localization. On bivariate analysis, there was no difference in terms of margin positivity (37.8% vs. 28.0% vs. 28.6%, P = .339) nor re-excision rates (13.3% vs. 12.0% vs. 14.3%, P = .961) for the WL, RS, and SS groups, respectively. Further, the volume of tissue removed was not significantly different between the 3 groups (71.9 cm3 vs. 55.8 cm3 vs. 86.6 cm3 for the WL, RS, and SS groups, respectively, P = .340). On multivariate analysis, margin status was affected by tumor size (OR = 1.336; 95% CI: 1.148-1.554, P<.001) but not by type of localization (P = .670). CONCLUSIONS: While there are a number of methods for tumor localization, choice of technique does not seem to influence volume of tissue resected nor margin status.

Are we choosing wisely? Drivers of preoperative MRI use in breast cancer patients.

INTRODUCTION: Factors contributing to the use of preoperative MRI remain poorly understood. METHODS: Data from a randomized controlled trial of stage 0-3 breast cancer patients undergoing breast conserving surgery between 2016 and 2018 were analyzed. RESULTS: Of the 396 patients in this trial, 32.6% had a preoperative MRI. Patient age, race, ethnicity, tumor histology, and use of neoadjuvant therapy were significant predictors of MRI use. On multivariate analysis, younger patients with invasive lobular tumors were more likely to have a preoperative MRI. Rates also varied significantly by individual surgeon (p < 0.001); in particular, female surgeons (39.9% vs. 24.0% for male surgeons, p = 0.001) and those in community practice (58.9% vs. 14.2% for academic, p < 0.001) were more likely to order preoperative MRI. Rates declined over the two years of the study, particularly among female surgeons. CONCLUSIONS: Preoperative MRI varies with patient age and tumor histology; however, there remains variability by individual surgeon.

Community-Based Breast Cancer Screening Using Digital Breast Tomosynthesis Versus Digital Mammography: Comparison of Screening Performance and Tumor Characteristics.

BACKGROUND. Prior studies comparing cancer screening by digital breast tomosynthesis (DBT) and digital mammography (DM) have largely entailed prospective trials and investigations at tertiary academic centers, which may encounter high-risk patient populations and lack heterogeneity among interpreting radiologists. Thus, results may not generalize across real-world community settings in the United States. OBJECTIVE. The purpose of this study was to compare DBT and DM in terms of screening performance and tumor characteristics of screen-detected cancers in a community practice setting. METHODS. Data were retrospectively retrieved for all screening mammography examinations performed by DBT or DM at four outpatient private practice facilities from January 1, 2012, to July 10, 2019. Examinations were interpreted by one of 26 radiologists (21 breast radiologists, five general radiologists). Further detailed information was recorded from radiology and pathology reports for all screen-detected cancers. Statistical comparisons were performed between DBT and DM in terms of screening performance and tumor characteristics of screen-detected cancers. RESULTS. A total of 310 cancers were detected in 47,096 screening DBT examinations and 83,200 screening DM examinations. Cancer detection rate was higher (p < .001) for DBT (3.4 per 1000 women) than for DM (1.8 per 1000 women). PPV1 was higher (p < .001) for DBT (3.5% [161/4641]) than for DM (2.1% [149/7116]). Patients with DBT-detected cancer were younger than those with DM-detected cancer (mean age [range], 61 years [40-87 years] vs 64 years [37-88 years]; p = .02). A greater percentage of DBT-detected than DM-detected cancers were invasive (85.1% [137/161] vs 72.5% [108/149]; p = .006), grade 1 when invasive (27.9% [38/136] vs 17.8% [19/107]; p = .04), and node negative (92.2% [71/77] vs 78.4% [58/74]; p = .02). Cancers detected by DBT and DM were not significantly different in histologic subtype, molecular subtype, or mean size (all p > .05). CONCLUSION. DBT showed a higher cancer detection rate and PPV1 than DM, and patients were younger at cancer diagnosis with DBT. Cancers detected on DBT were more often invasive, grade 1, and node negative. CLINICAL IMPACT. The findings support the generalizability of insights into DBT-based screening, which previously have been investigated primarily in academic settings.

Factors Affecting Time to Surgery in Breast Cancer Patients.

BACKGROUND: We sought to determine factors affecting time to surgery (TTS) to identify potential modifiable factors to improve timeliness of care. METHODS: Patients with clinical stage 0-3 breast cancer undergoing partial mastectomy in 2 clinical trials, conducted in ten centers across the US, were analyzed. No preoperative workup was mandated by the study; those receiving neoadjuvant therapy were excluded. RESULTS: The median TTS among the 583 patients in this cohort was 34 days (range: 1-289). Patient age, race, tumor palpability, and genomic subtype did not influence timeliness of care defined as TTS ≤30 days. Hispanic patients less likely to have a TTS ≤30 days (P = .001). There was significant variation in TTS by surgeon (P < .001); those practicing in an academic center more likely to have TTS ≤30 days than those in a community setting (55.1% vs 19.3%, P < .001). Patients who had a preoperative ultrasound had a similar TTS to those who did not (TTS ≤30 days 41.9% vs 51.9%, respectively, P = .109), but those who had a preoperative MRI had a significantly increased TTS (TTS ≤30 days 25.0% vs 50.9%, P < .001). On multivariate analysis, patient ethnicity was no longer significantly associated with TTS ≤30 (P = .150). Rather, use of MRI (OR: .438; 95% CI: .287-.668, P < .001) and community practice type (OR: .324; 95% CI: .194-.541, P < .001) remained independent predictors of lower likelihood of TTS ≤30 days. CONCLUSIONS: Preoperative MRI significantly increases time to surgery; surgeons should consider this in deciding on its use.

Impact of Cavity Shave Margins on Margin Status in Patients with Pure Ductal Carcinoma In Situ.

BACKGROUND: We examined the impact of cavity shave margins (CSMs) on margin status in patients with pure ductal carcinoma in situ (DCIS) undergoing partial mastectomy (PM). METHODS: One hundred and nine patients from 2 multicenter, randomized controlled trials were identified with pure DCIS (no invasive cancer). Surgeons performed their best PM, with specimen radiography and resection of selective margins per surgeon discretion. Patients were then randomized to have CSM resected or not. A positive margin was defined as <2 mm from ink. RESULTS: Median patient age was 63 years; median size of DCIS was 1.20 cm; 43.6% of patients had high-grade DCIS; and 58 (53.2%) patients were randomized to take CSM. The "shave" and "no-shave" groups were well-matched for age, race, ethnicity, palpability, grade, and size of DCIS. Although 33 (56.9%) of the patients in the shave group had a positive margin before randomization, only 12 (20.7%) had a positive margin after randomization to CSM (p < 0.001). In the no-shave group, 17 patients (33.3%) had a positive margin. Controlling for size and grade of DCIS, taking CSM resulted in a nearly 65% reduction in the positive-margin rate (odds ratio 0.366; 95% CI, 0.136 to 0.981; p = 0.046). Size of DCIS remained an independent predictor of positive margins in the model (odds ratio 1.646; 95% CI, 1.227 to 2.209; p = 0.001). CONCLUSIONS: CSM reduces positive-margin rates in patients with pure DCIS, and can be a practical solution for DCIS patients who tend to have a high rate of margin positivity.

Resection of Cavity Shave Margins in Stage 0-III Breast Cancer Patients Undergoing Breast Conserving Surgery: A Prospective Multicenter Randomized Controlled Trial.

OBJECTIVE: Single-center studies have demonstrated that resection of cavity shave margins (CSM) halves the rate of positive margins and re-excision in breast cancer patients undergoing partial mastectomy (PM). We sought to determine if these findings were externally generalizable across practice settings. METHODS: In this multicenter randomized controlled trial occurring in 9 centers across the United States, stage 0-III breast cancer patients undergoing PM were randomly assigned to either have resection of CSM ("shave" group) or not ("no shave" group). Randomization occurred intraoperatively, after the surgeon had completed their standard PM. Primary outcome measures were positive margin and re-excision rates. RESULTS: Between July 28, 2016 and April 13, 2018, 400 patients were enrolled in this trial. Four patients (2 in each arm) did not meet inclusion criteria after randomization, leaving 396 patients for analysis: 196 in the "shave" group and 200 to the "no shave" group. Median patient age was 65 years (range; 29-94). Groups were well matched at baseline for demographic and clinicopathologic factors. Prior to randomization, positive margin rates were similar in the "shave" and "no shave" groups (76/196 (38.8%) vs. 72/200 (36.0%), respectively, P = 0.604). After randomization, those in the "shave" group were significantly less likely than those in the "no shave" group to have positive margins (19/196 (9.7%) vs. 72/200 (36.0%), P < 0.001), and to require re-excision or mastectomy for margin clearance (17/196 (8.7%) vs. 47/200 (23.5%), P < 0.001). CONCLUSION: Resection of CSM significantly reduces positive margin and re-excision rates in patients undergoing PM.

A Three-Dimensional Bioabsorbable Tissue Marker for Volume Replacement and Radiation Planning: A Multicenter Study of Surgical and Patient-Reported Outcomes for 818 Patients with Breast Cancer.

BACKGROUND: Accurate identification of the tumor bed after breast-conserving surgery (BCS) ensures appropriate radiation to the tumor bed while minimizing normal tissue exposure. The BioZorb® three-dimensional (3D) bioabsorbable tissue marker provides a reliable target for radiation therapy (RT) planning and follow-up evaluation while serving as a scaffold to maintain breast contour. METHODS: After informed consent, 818 patients (826 breasts) implanted with the BioZorb® at 14 U.S. sites were enrolled in a national registry. All the patients were prospectively followed with the BioZorb® implant after BCS. The data collected at 3, 6, 12, and 24 months included all demographics, treatment parameters, and provider/patient-assessed cosmesis. RESULTS: The median follow-up period was 18.2 months (range, 0.2-53.4 months). The 30-day breast infection rate was 0.5 % of the patients (n = 4), and re-excision was performed for 8.1 % of the patients (n = 66), whereas 2.6 % of the patients (n = 21) underwent mastectomy. Two patients (0.2 %) had local recurrence. The patient-reported cosmetic outcomes at 6, 12, and 24 months were rated as good-to-excellent by 92.4 %, 90.6 %, and 87.3 % of the patients, respectively and similarly by the surgeons. The radiation oncologists reported planning of target volume (PTV) reduction for 46.2 % of the patients receiving radiation boost, with PTV reduction most commonly estimated at 30 %. CONCLUSIONS: This report describes the first large multicenter study of 818 patients implanted with the BioZorb® tissue marker during BCS. Radiation oncologists found that the device yielded reduced PTVs and that both the patients and the surgeons reported good-to-excellent long-term cosmetic outcomes, with low adverse effects. The BioZorb® 3D tissue marker is a safe adjunct to BCS and may add benefits for both surgeons and radiation oncologists.

Nipple pain: Raynaud's beyond fingers and toes.

Raynaud's phenomenon of the nipple (RPN) is a cause of nipple pain scarcely reported in the literature and frequently missed by physicians. We present a case of RPN in a pregnant mother who sought breast surgical consultation for episodic nipple pain. Review of the literature reveals RPN is predominant in lactating and pregnant patients and missed diagnosis can cause cessation of breastfeeding or mistreatment with antifungals. Clinical suspicion should be raised if symptoms are precipitated by cold, associated with color change, occur during pregnancy or breastfeeding, or with a history of Raynaud's. Treatment is generally supportive, with nifedipine used for severe cases.

Breast-Specific Sensuality and Appearance Satisfaction: Comparison of Breast-Conserving Surgery and Nipple-Sparing Mastectomy.

BACKGROUND: We demonstrated previously that lumpectomy (L) patients reported higher appearance satisfaction, appreciation of a pleasurable breast caress, and persistence of the breast during intimacy than mastectomy with reconstruction, which we used to describe breast-specific sensuality. Our current objective was to compare breast-specific sensuality between L and nipple-sparing mastectomy (NSM). DESIGN: An anonymous, cross-sectional survey was distributed to breast cancer survivors between 2014 and 2016. Eligible patients underwent operation between 2000 and 2014, were adults older than 18 years, English-speaking, and at least one year into the post-operative period. Demographic characteristics, treatment details, Female Sexual Function Index metrics, and investigator-generated questions about appearance satisfaction and breast-specific sensuality were collected. RESULTS: Of the 600 women who participated, 585 surveys were eligible. Surgical modality was reported as L by 406 (69.4%), mastectomy alone by 50 (8.5%), and mastectomy with reconstruction by 129 (22.1%). Nipple-preservation data were available for 47 of 129 mastectomy with reconstruction patients (36.4%), with 21 NSM and 26 non-nipple-sparing mastectomy patients. Favorable postoperative appearance satisfaction was reported by 76.2% of L and 71.4% of NSM (p = 0.039). Lumpectomy patients reported feeling more comfortable being seen undressed than NSM patients (82.4% vs 71.4%; p = 0.0003). The chest remained a part of intimacy for 65.4% of L patients vs 42.9% of NSM patients (p = 0.0009). A pleasurable breast caress was reported more frequently by L patients than NSM patients (66.2% vs 20%; p ≤ 0.0001). The breast caress was unpleasant for 40% of NSM patients, nearly 4-fold higher than L patients (11.3%; p < 0.0001). CONCLUSIONS: NSM patients were significantly less satisfied with appearance, less comfortable being seen undressed, had decreased persistence of breast intimacy, and experienced a less pleasurable breast caress than L patients. Counseling patients about these findings will empower informed decision making, optimize expectations, and can enhance postoperative satisfaction.

Breast-Specific Sensuality and Sexual Function in Cancer Survivorship: Does Surgical Modality Matter?

PURPOSE: More early-staged breast cancer patients are choosing mastectomy. No studies have addressed breast-specific sensuality (BSS), defined as the breast's role during intimacy. We explored BSS among women undergoing lumpectomy (L), mastectomy alone (M), or with reconstruction (MR) and analyzed the association of surgical modality with sexual function. METHODS: Women undergoing breast cancer surgery between 2000 and 2013 were eligible for survey using investigator-generated questions and the Female Sexual Function Index (FSFI). Demographic and surgical data were collected by chart review. The Kruskal-Wallis test was used to analyze FSFI scores, and χ 2 or Fisher's exact tests were used for categorical data. RESULTS: Of 453 invited participants, 268 (59%) completed the survey. Of these, 69.4, 22.4, and 8.2% underwent L, MR, or M, respectively. The importance of the breast/chest wall during intimacy declined significantly regardless of surgical modality (L 83-74%, p = 0.0006; M 95-47%, p = 0.003; MR 93-77%, p = 0.002). No difference in sexual function was found between L, MR, and M (median FSFI score 28.2, 27.5, 25.9, respectively; p = 1.0). Comparing L versus MR, higher FSFI scores resulted with appearance satisfaction (29.0 vs. 22.6 p = 0.002) and preserved BSS as pleasurable breast caress (28.8 vs. 26.5, p = 0.04) and the breast as part of intimacy (28.8 vs. 24.8, p = 0.1). CONCLUSIONS: Breast cancer surgery is associated with lowered BSS. However, BSS and appearance satisfaction scores are better for L and appear to correlate with improved sexual function postoperatively. These data may guide surgical counseling and contribute to survivorship outcomes.