Ipsilateral Breast Cancer Research Articles

Mastectomy options for the treatment of ipsilateral breast cancer recurrence after lumpectomy

BackgroundMastectomy is the recommended treatment for ipsilateral breast tumor recurrence (IBTR) in patients who initially received breast conservation surgery (BCS) and radiation. We evaluated the 3 types of mastectomies performed for the surgical treatment of IBTR (nipple sparing (NSM), skin sparing (SSM) and total mastectomy (TM)) to assess surgical complications and local control outcomes among groups. MethodsPatients who developed IBTR after BCS and received mastectomy from 2011 to 2019 were reviewed. Patient characteristics and treatment were analyzed. The incidence of postoperative complications and second breast cancer recurrence were compared. ResultsMastectomy was performed in 113 patients presenting with isolated IBTR (17 NSM, 48 SSM and 48 TM). There was no difference in post-operative complications between groups. At 3-year follow-up, 5 (4%) patients had a second recurrence. Tumor size at IBTR was the only predictor for second recurrence and not mastectomy type or receipt of reconstruction. ConclusionIn patients initially treated with BCS who experienced an IBTR, NSM or SSM mastectomy with immediate reconstruction had low complication rates and no increase in local recurrence compared to the TM group

Classification of MR-Detected Additional Lesions in Patients With Breast Cancer Using a Combination of Radiomics Analysis and Machine Learning.

ObjectiveThis study was conducted in order to investigate the feasibility of using radiomics analysis (RA) with machine learning algorithms based on breast magnetic resonance (MR) images for discriminating malignant from benign MR-detected additional lesions in patients with primary breast cancer.Materials and MethodsOne hundred seventy-four MR-detected additional lesions (benign, n = 86; malignancy, n = 88) from 158 patients with ipsilateral primary breast cancer from a tertiary medical center were included in this retrospective study. The entire data were randomly split to training (80%) and independent test sets (20%). In addition, 25 patients (benign, n = 21; malignancy, n = 15) from another tertiary medical center were included for the external test. Radiomics features that were extracted from three regions-of-interest (ROIs; intratumor, peritumor, combined) using fat-saturated T1-weighted images obtained by subtracting pre- from postcontrast images (SUB) and T2-weighted image (T2) were utilized to train the support vector machine for the binary classification. A decision tree method was utilized to build a classifier model using clinical imaging interpretation (CII) features assessed by radiologists. Area under the receiver operating characteristic curve (AUROC), accuracy, sensitivity, and specificity were used to compare the diagnostic performance.ResultsThe RA models trained using radiomics features from the intratumor-ROI showed comparable performance to the CII model (accuracy, AUROC: 73.3%, 69.6% for the SUB RA model; 70.0%, 75.1% for the T2 RA model; 73.3%, 72.0% for the CII model). The diagnostic performance increased when the radiomics and CII features were combined to build a fusion model. The fusion model that combines the CII features and radiomics features from multiparametric MRI data demonstrated the highest performance with an accuracy of 86.7% and an AUROC of 91.1%. The external test showed a similar pattern where the fusion models demonstrated higher levels of performance compared with the RA- or CII-only models. The accuracy and AUROC of the SUB+T2 RA+CII model in the external test were 80.6% and 91.4%, respectively.ConclusionOur study demonstrated the feasibility of using RA with machine learning approach based on multiparametric MRI for quantitatively characterizing MR-detected additional lesions. The fusion model demonstrated an improved diagnostic performance over the models trained with either RA or CII alone.

Axillary metastasis from occult breast cancer and synchronous contralateral breast cancer initially suspected to be cancer with contralateral axillary metastasis: a case report

BackgroundInitial detection of axillary metastasis without known ipsilateral breast cancer could be a challenging diagnostic problem. Four options could be considered for the primary site of the malignancy: ipsilateral occult breast cancer, contralateral breast cancer, tumors in other distant organs, and primary axillary malignancy itself. Although breast cancer is known as the most common primary cancer of axillary metastasis, both occult breast cancer and breast cancer with contralateral axillary metastasis (CAM) are rare.Case presentationA 63-year-old woman presented with palpable right axillary metastasis, and a tiny contralateral breast cancer was detected by breast magnetic resonance imaging. No lesion was found in the ipsilateral right breast and contralateral left axillary region. Both right axillary metastasis and contralateral breast cancer were positive for estrogen receptor. The diagnostic issue was to determine whether the axillary metastasis was derived from the contralateral breast cancer or not. Right axillary dissection and left breast conserving surgery were performed. The final diagnosis was occult breast cancer that presented with axillary lymph node metastasis and early-stage synchronous contralateral breast cancer, based on clinical evidence and postoperative pathologic results. After surgery, systemic treatment and whole breast irradiation were administered. No recurrence or metastasis was observed 15 months postoperatively.ConclusionFor accurate diagnosis of axillary metastasis without detectable ipsilateral breast cancer, multifaceted diagnostic approach considering clinical, radiological, and pathological evidences is required.

The Feasibility of Radiation Therapy after Breast-Conserving Surgery for Multiple Ipsilateral Breast Cancer: An Initial Report from ACOSOG Z11102 (Alliance) Trial

Purpose:Historically, multiple ipsilateral breast cancer (MIBC) has been a contraindication to breast-conserving therapy. We report the feasibility of radiation therapy (RT) after breast-conserving therapy in MIBC from the Alliance Z11102 trial.Methods and Materials:Delineation of targets and organs at risk was performed according to the Radiation Therapy Oncology Group contouring consensus definitions. RT was delivered to the whole breast to 45 to 50 Gy in standard daily fractions of 1.8 to 2.0 Gy. A boost of 10 to 16 Gy in 2.0-Gy daily fractions to each tumor bed was mandatory.Results:A total of 236 eligible patients were enrolled in the study between July 23, 2012 and August 19, 2016. Of those, 195 (83%) completed RT. No patient underwent mastectomy for failure to meet the RT dose constraints. Higher absolute boost volume was associated with increased incidence of grade 2 or higher dermatitis (odds ratio, 1.21; 95% confidence interval, 1.041.41; P = .014). Higher relative boost volume as a percentage of the overall breast volume was not associated with increased dermatitis. Neither absolute nor relative boost volume appeared to significantly influence overall cosmesis.Conclusions:Breast conservation followed by whole breast RT plus boost to each tumor bed was feasible in the majority of patients with MIBC. Increasing radiation boost volume was associated with increased incidence of acute dermatitis, but was not associated with worse overall cosmesis.

PR77 - BREAST CONSERVING SURGERY VERSUS SALVAGE MASTECTOMY FOR IPSILATERAL BREAST CANCER RECURRENCE: A PROPENSITY SCORE MATCHING ANALYSIS

Salvage mastectomy is regarded as the treatment of first choice for ipsilateral breast cancer recurrence (IBCR), even if a second breast conserving surgery (BCS) is feasible. The purpose of this study was to compare the long-term oncological outcomes of IBCR patients who had undergone either mastectomy or second BCS, performing a propensity score matching (PSM) analysis to reduce the selection bias. All the consecutive patients with IBCR were retrospectively reviewed and divided into two different groups of treatment: repeat BCS versus salvage mastectomy. The propensity score predicting the probability of surgical treatment was determined for each patient and a 1:1 matching was performed. Disease-free survival (DFS), distant disease-free survival (DDFS), overall survival (OS), and breast cancer-specific survival (BCSS) were analyzed and compared between the two groups. A total of 309 patients underwent surgical treatment for IBCR. After PSM, 108 patients treated with repeat BCS and 108 patients treated with salvage mastectomy were included in the analysis. There was no significant difference in terms of DFS between patients with IBCR receiving repeat BCS or salvage mastectomy (p = 0.167). However, patients with IBCR undergoing second BCS had significantly better DDFS, OS, and BCSS compared to salvage mastectomy (p < 0.001). Salvage mastectomy should not be considered the optimal treatment for IBCR and it does not seem to improve prognosis compared to repeat conserving surgery. Second BCS for IBCR is a safe option with encouraging long-term oncological outcomes and should be proposed to all patients, when technically feasible.

Long-term risk of subsequent ipsilateral lesions after surgery with or without radiotherapy for ductal carcinoma in situ of the breast

BackgroundRadiotherapy (RT) following breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) reduces ipsilateral breast event rates in clinical trials. This study assessed the impact of DCIS treatment on a 20-year risk of ipsilateral DCIS (iDCIS) and ipsilateral invasive breast cancer (iIBC) in a population-based cohort.MethodsThe cohort comprised all women diagnosed with DCIS in the Netherlands during 1989–2004 with follow-up until 2017. Cumulative incidence of iDCIS and iIBC following BCS and BCS + RT were assessed. Associations of DCIS treatment with iDCIS and iIBC risk were estimated in multivariable Cox models.ResultsThe 20-year cumulative incidence of any ipsilateral breast event was 30.6% (95% confidence interval (CI): 28.9–32.6) after BCS compared to 18.2% (95% CI 16.3–20.3) following BCS + RT. Women treated with BCS compared to BCS + RT had higher risk of developing iDCIS and iIBC within 5 years after DCIS diagnosis (for iDCIS: hazard ratio (HR)age < 50 3.2 (95% CI 1.6–6.6); HRage ≥ 50 3.6 (95% CI 2.6–4.8) and for iIBC: HRage<50 2.1 (95% CI 1.4–3.2); HRage ≥ 50 4.3 (95% CI 3.0–6.0)). After 10 years, the risk of iDCIS and iIBC no longer differed for BCS versus BCS + RT (for iDCIS: HRage < 50 0.7 (95% CI 0.3–1.5); HRage ≥ 50 0.7 (95% CI 0.4–1.3) and for iIBC: HRage < 50 0.6 (95% CI 0.4–0.9); HRage ≥ 50 1.2 (95% CI 0.9–1.6)).ConclusionRT is associated with lower iDCIS and iIBC risk up to 10 years after BCS, but this effect wanes thereafter.

Preferences of Treatment Strategies among Women with Low-Risk DCIS and Oncologists.

Simple SummaryPreferences for treatment strategies for low-risk ductal carcinoma in situ (DCIS), a potential precursor of invasive breast cancer (IBC) including a new active surveillance strategy, were elicited with a discrete choice experiment among recently-diagnosed women and oncologists involved in the care of women with DCIS. Patients exhibited strong preferences for active surveillance and seemed prepared to accept much higher levels of 10-year risk of developing ipsilateral invasive breast cancer than oncologists. Both patients and oncologists showed a strong aversion toward more extensive locoregional treatments (i.e., breast conserving surgery followed by radiotherapy, and mastectomy), while both groups demonstrated a strong preference toward shorter follow-up intervals.As ongoing trials study the safety of an active surveillance strategy for low-risk ductal carcinoma in situ (DCIS), there is a need to explain why particular choices regarding treatment strategies are made by eligible women as well as their oncologists, what factors enter the decision process, and how much each factor affects their choice. To measure preferences for treatment and surveillance strategies, women with newly-diagnosed, primary low-risk DCIS enrolled in the Dutch CONTROL DCIS Registration and LORD trial, and oncologists participating in the Dutch Health Professionals Study were invited to complete a discrete choice experiment (DCE). The relative importance of treatment strategy-related attributes (locoregional intervention, 10-year risk of ipsilateral invasive breast cancer (iIBC), and follow-up interval) were discerned using conditional logit models. A total of n = 172 patients and n = 30 oncologists completed the DCE. Patient respondents had very strong preferences for an active surveillance strategy with no surgery, irrespective of the 10-year risk of iIBC. Extensiveness of the locoregional treatment was consistently shown to be an important factor for patients and oncologists in deciding upon treatment strategies. Risk of iIBC was least important to patients and most important to oncologists. There was a stronger inclination toward a twice-yearly follow-up for both groups compared to annual follow-up.

Multidisciplinary Review of Intraductal Papilloma of the Breast can Identify Patients who may Omit Surgical Excision.

The purpose of this study was to define contemporary management recommendations regarding who would benefit from surgical excision of intraductal papilloma (IDP). A prospective database from a single institution identified patients with IDP on percutaneous biopsy from February 2015 to September 2020. Categorical patient demographic, biopsy, and pathologic variables were analyzed using Fisher's exact test and continuous demographic and imaging variables using the Mann-Whitney U test. IDP was present in 416 biopsies, at a median age of 56 years. The median size was 0.9cm, and the majority had greater than 50% of the target excised by biopsy. Surgical excision was performed for 124 of 416 biopsies (29.8%). Upgrade to malignancy was identified in 14 (11.3%): 8 to ductal carcinoma in situ (DCIS) and 6 to invasive cancer. Upgrade was significantly associated with concurrent ipsilateral breast cancer (p = 0.027), larger imaging size (p = 0.045), <50% excised with biopsy (p = 0.02), and atypia involving IDP (p = 0.045). Age, clinical presentation, and concurrent contralateral cancer were not significantly associated with upgrade. Lowest upgrade risk (0%) was in pure IDP ≤1 cm with >50% removed by biopsy. Of 401 biopsies that either did not upgrade or undergo excision, 7 (1.7%) developed subsequent breast cancer over a median follow-up of 23.5 months (interquartile range [IQR] 11,41), none at IDP site. After multidisciplinary review, the management of IDP can be stratified into low- and high-risk for upgrade groups using key criteria. Low-risk group may omit surgical excision, because those patients have 0% risk of upgrade over the limited short-term follow-up.

How Protective are Nipple-Sparing Prophylactic Mastectomies in BRCA1 and BRCA2 Mutation Carriers?

Nipple-sparing mastectomy (NSM) is now routinely offered to BRCA mutation carriers for risk reduction. We assessed the rates of ipsilateral cancer events after prophylactic and therapeutic NSM in BRCA1 and BRCA2 mutation carriers. BRCA1 and BRCA2 mutation carriers undergoing NSM from October 2007 to June 2019 were identified in a single-institution prospective database, with variants of unknown significance being excluded. Patient, tumor, and outcomes data were collected. Follow-up analysis was by cumulative breast-years (total years of follow-up of each breast) and woman-years (total years of follow-up of each woman). Overall, 307 BRCA1 and BRCA2 mutation carriers (160 BRCA1, mean age 41.4years [range 21-65]; and 147 BRCA2, mean age 43.8years [range 23-65]) underwent 607 NSMs, with a median follow-up of 42 months (range 1-143). 388 bilateral prophylactic NSMs had 744 cumulative woman-years of follow-up, with no new cancers seen (< 0.0013 new cancers per woman-years); 251 BRCA1 prophylactic NSMs had 1034 cumulative breast-years of follow-up, with no new ipsilateral cancers seen (< 0.0010 per breast-year); 66 BRCA1 therapeutic NSMs had 328 cumulative breast-years of follow-up, with one ipsilateral cancer recurrence not directly involving the nipple or areola (0.0030 per breast-year); 237 BRCA2 prophylactic NSMs had 926 cumulative breast-years of follow-up, with no new ipsilateral cancers seen (< 0.0011 per breast-year); and 53 BRCA2 therapeutic NSMs had 239 cumulative breast-years of follow-up, with two ipsilateral recurrent cancers, neither of which directly involved the nipple or areola (0.0084 per breast-year). The risk of new ipsilateral breast cancers is extremely low after NSM in BRCA1 and BRCA2 mutation carriers. NSM is an effective risk-reducing strategy for BRCA gene mutations.

Preoperative diagnosis of BRCA1/2 mutation impacts decision-making for risk-reducing mastectomy in breast cancer patients

Decision to undergo risk-reducing mastectomy (RRM) needs to consider several factors, including patient’s preference, surgeon’s preference, family history, and genetic predisposition. The aim of this study was to examine whether preoperative diagnosis of BRCA1/2 mutation status could influence surgical decision-making in newly diagnosed breast cancer patients. We retrospectively reviewed ipsilateral breast cancer patients with BRCA1/2 mutation who underwent primary surgery between January 2008 and November 2019 at a single institution in Korea. Of 344 eligible patients, 140 (40.7%) patients were aware of their mutation status ‘prior to surgery’, while 204 (59.3%) did not. Contralateral RRM rate was significantly higher in the group with BRCA1/2 mutation status identified ‘prior to surgery’ compared to the group with mutation status identified ‘after surgery’ [45.0% (63/140) vs. 2.0% (4/204)] (p < 0.001). Reduced turnaround time of BRCA1/2 testing (p < 0.001) and the use of neoadjuvant chemotherapy (p < 0.001) were associated with BRCA1/2 mutation status identified prior to surgery. Although not statistically significant, higher incidence of developing contralateral breast cancer for BRCA1/2 mutation carriers who underwent ipsilateral surgery-only compared to those who underwent contralateral RRM was observed [12.1% (95% CI: 7.7–17.7%)] (p = 0.1618). Preoperative diagnosis of BRCA1/2 mutation could impact surgical decision-making for breast cancer patients to undergo risk-reducing surgery at the time of initial surgery.

Breast conserving surgery versus salvage mastectomy for ipsilateral breast cancer recurrence: a propensity score matching analysis.

Salvage mastectomy is regarded as the treatment of first choice for ipsilateral breast cancer recurrence (IBCR), even if a second breast conserving surgery (BCS) is feasible. The purpose of this study was to compare the long-term oncological outcomes of IBCR patients who had undergone either mastectomy or second BCS, performing a propensity score matching (PSM) analysis to reduce the selection bias. All the consecutive patients with IBCR were retrospectively reviewed and divided into two different groups of treatment: repeat BCS versus salvage mastectomy. The propensity score predicting the probability of surgical treatment was determined for each patient and a 1:1 matching was performed. Disease-free survival (DFS), distant disease-free survival (DDFS), overall survival (OS), and breast cancer-specific survival (BCSS) were analyzed and compared between the two groups. A total of 309 patients underwent surgical treatment for IBCR. After PSM, 108 patients treated with repeat BCS and 108 patients treated with salvage mastectomy were included in the analysis. There was no significant difference in terms of DFS between patients with IBCR receiving repeat BCS or salvage mastectomy (p = 0.167). However, patients with IBCR undergoing second BCS had significantly better DDFS, OS, and BCSS compared to salvage mastectomy (p < 0.001). Salvage mastectomy should not be considered the optimal treatment for IBCR and it does not seem to improve prognosis compared to repeat conserving surgery. Second BCS for IBCR is a safe option with encouraging long-term oncological outcomes and should be proposed to all patients, when technically feasible.

Ten years follow-up of histologically benign calcifications in the breast after vacuum-assisted stereotactic biopsy (VASB): Is additional mammographic follow-up warranted?

ObjectiveThis study assessed the short-term and the long-term breast cancer rate in patients with benign histopathologic results after a vacuum-assisted stereotactic biopsy (VASB) for calcifications. MethodsIn a retrospective cohort study, all consecutive patients who had a benign diagnosis after VASB to analyze breast calcifications. Data of breast cancer development at short-term (four years) and long-term follow-up was gathered. Breast cancer rates in our cohort were compared to the breast cancer incidence in the general population. ResultsOf 1376 patients who underwent VASB to analyze breast calcifications, 823 had a benign histopathologic diagnosis. During short-term follow-up, eight patients developed breast cancer. During the mean long-term follow-up period of 9.3 ± 3.1 years, 22 patients were diagnosed with ipsilateral breast cancer. The incidence rate of breast cancer after benign biopsy was comparable to the rate in the general population. ConclusionIn patients with VASB-confirmed benign calcifications of the breast, we found no excess incidence of ipsilateral breast cancer during ten years follow-up. Therefore, in patients with an increased risk of breast cancer (due to a history of breast cancer or familial risk) annual mammography should be sufficient. Patients with a population-based risk may be monitored via biennial mammography by the national screening program. More frequent screening would provide no benefit.

Disparities in surveillance imaging after breast conserving surgery for primary DCIS.

6516 Background: Due to the elevated risk of ipsilateral invasive breast cancer (iIBC) after diagnosis with primary ductal carcinoma in situ (DCIS), professional guidelines recommend surveillance screening within 6-12 months (mo) after completion of initial local treatment and annually thereafter. To characterize adherence to these guidelines, we explored longitudinal patterns of utilization and factors associated with the use of surveillance imaging (mammography, MRI, ultrasound) for women with primary DCIS treated with breast conserving surgery (BCS) ± radiotherapy (RT) within 6 mo of diagnosis. Methods: A treatment-stratified random sample of patients diagnosed with screen-detected and biopsy-confirmed DCIS in 2008-15 was selected from 1,330 Commission on Cancer-accredited facilities (up to 20/site) in the US. All imaging exams coded as asymptomatic were collected from 6 mo up to 10 years (yr) post-diagnosis. Time was defined according to 12-mo long surveillance periods. To be included in a given surveillance period, women had to be alive and free of a new breast cancer diagnosis through the end of the period. Women were classified as “consistent” screeners if they had at least one surveillance screen during each period, for the first 5 yr post-treatment or until censoring, whichever occurred first. Repeated measures multivariable logistic regression with generalized estimating equations was used to model receipt of surveillance breast imaging over time. The model included clinical and socioeconomic features. Results: The final analytic cohort contained 12,559 women; 8,989 (71.6%) received RT after BCS. Median age was 60 yr (interquartile range: 52-69) and median follow-up was 5.6 yr (95% confidence interval [CI] 5.6-5.7). Among women who received BCS (instead of BCS+RT), 62.5% (79.7%) underwent surveillance imaging within 6-18 mo after diagnosis. 38.7% (54.0%) were categorized as “consistent” screeners. Compared to white women, Black women were less likely to receive surveillance screening after treatment for primary DCIS (odds ratio [OR] 0.85, 95% CI 0.77-0.94). Hispanic ethnicity had a similar association (OR 0.86, 95% CI 0.74-0.99) compared to non-Hispanic ethnicity. Women with private insurance, compared to government insurance, were more likely to receive screening (OR 1.20, 95% CI 1.11-1.30). Prognostic tumor features indicative of a higher risk of subsequent iIBC, including higher grade, presence of comedonecrosis, and hormone receptor-negative DCIS, were not associated with screening uptake. Conclusions: Despite guidelines recommending annual surveillance imaging, many women with primary DCIS do not undergo regular imaging after BCS. The findings from this US-based study suggest that disparities in screening uptake are associated with race/ethnicity and insurance status rather than prognostic tumor features.

Breast adipocyte size associates with ipsilateral invasive breast cancer risk after ductal carcinoma in situ

Although ductal carcinoma in situ (DCIS) is a non-obligate precursor to ipsilateral invasive breast cancer (iIBC), most DCIS lesions remain indolent. Hence, overdiagnosis and overtreatment of DCIS is a major concern. There is an urgent need for prognostic markers that can distinguish harmless from potentially hazardous DCIS. We hypothesised that features of the breast adipose tissue may be associated with risk of subsequent iIBC. We performed a case–control study nested in a population-based DCIS cohort, consisting of 2658 women diagnosed with primary DCIS between 1989 and 2005, uniformly treated with breast conserving surgery (BCS) alone. We assessed breast adipose features with digital pathology (HALO®, Indica Labs) and related these to iIBC risk in 108 women that developed subsequent iIBC (cases) and 168 women who did not (controls) by conditional logistic regression, accounting for clinicopathological and immunohistochemistry variables. Large breast adipocyte size was significantly associated with iIBC risk (odds ratio (OR) 2.75, 95% confidence interval (95% CI) = 1.25–6.05). High cyclooxygenase (COX)-2 protein expression in the DCIS cells was also associated with subsequent iIBC (OR 3.70 (95% CI = 1.59–8.64). DCIS with both high COX-2 expression and large breast adipocytes was associated with a 12-fold higher risk (OR 12.0, 95% CI = 3.10–46.3, P < 0.001) for subsequent iIBC compared with women with smaller adipocyte size and low COX-2 expression. Large breast adipocytes combined with high COX-2 expression in DCIS is associated with a high risk of subsequent iIBC. Besides COX-2, adipocyte size has the potential to improve clinical management in patients diagnosed with primary DCIS.

Treatment of Ipsilateral Breast Cancer Recurrence (IBCR) after Breast Conservation Therapy (BCT)

AbstractIn-breast recurrence or ipsilateral breast cancer recurrence (IBCR) suspected by imaging or palpation, second primary carcinoma and any distant metastases should be ruled out by core biopsy prior to breast surgery. The surgical standard in IBCR management is salvage mastectomy. Increasingly, however, patients express a justified desire for breast conservation in IBCR. In favourable relations of tumour and breast size, long interval between primary disease and IBCR recurrence, favourable tumour biology and ruled out distant metastases, re-BCT may be an option. As patients usually have undergone adjuvant radiotherapy already, re-radiotherapy (brachytherapy/percutaneous RT) should be explored. Systemic management must be based on tumour biology and prior treatment. While the risk of local recurrence increases following re-BCT, overall survival is not compromised.

P016 - Ipsilateral breast cancer recurrence: characteristics, treatment, and long-term oncological results at a high volume center

P016 - Ipsilateral breast cancer recurrence: characteristics, treatment, and long-term oncological results at a high volume center

Repeat breast-conserving treatment of ipsilateral breast cancer recurrence: a nationwide survey amongst breast surgeons and radiation oncologists in the Netherlands

BackgroundIn line with the paradigm to minimize surgical morbidity in patients with primary breast cancer, there is increasing evidence for the safety of a repeat breast-conserving treatment (BCT) of an ipsilateral breast tumour recurrence (IBTR) in selected patients. The conditions for the feasibility of a repeat BCT vary widely in literature. In clinical practice, many physicians have ongoing concerns about the oncological safety and possible toxicity of repeat BCT.AimTo investigate the attitude of Dutch breast surgeons and radiation oncologists towards repeat BCT and to report on their experiences with, objections against and perceived requirements to consider a repeat BCT in case of IBTR.Patients and methodsAn online survey consisting of a maximum of 26 open and multiple-choice questions about repeat BCT for IBTR was distributed amongst Dutch breast surgeons and radiation oncologists.ResultsForty-nine surgeons representing 49% of Dutch hospitals and 20 radiation oncologists representing 70% of Dutch radiation oncology centres responded. A repeat BCT was considered feasible in selected cases by 28.7% of breast surgeons and 55% of radiation oncologists. The most important factors to consider a repeat BCT for both groups were the patient’s preference to preserve the breast and surgical feasibility of a second lumpectomy. Arguments against a repeat BCT were based on the perceived unacceptable toxicity and cosmesis of a second course of radiotherapy. The technique of preference for re-irradiation would be partial breast irradiation (PBI) according to all radiation oncologists. Differentiating between new primary tumours (NPT) and true recurrences (TR) was reported to be done by 57.1% of breast surgeons and 60% of radiation oncologists. The most important reason to differentiate between NPT and TR was to establish prognosis and to consider whether a repeat BCT would be feasible.ConclusionAn increasing number of Dutch breast cancer specialists is considering a repeat BCT feasible in selected cases, at the patient’s preference and with partial breast re-irradiation.

Repeat Sentinel Lymph Node Surgery in Recurrent Breast Cancer: Peritumoral vs. Periareolar Injections

BackgroundIn the setting of recurrent cancer, there is no standard methodology regarding the technical aspects of repeat sentinel lymph node (rSLN) surgery. We analyzed our institutional experience with attempted rSLN surgery to determine the optimal injection technique. Materials and MethodsSingle site, retrospective review of patients with prior lumpectomy for breast cancer who presented with recurrent or new ipsilateral breast cancer and underwent attempt at rSLN surgery from 2008 to 2017. Patients with prior mastectomy or no prior ipsilateral axillary operation were excluded. ResultsA total of 141 patients were included; 103 (73%) underwent successful rSLN biopsy procedure. Lymphoscintigraphy showed aberrant drainage in 32 (26%). Periareolar (PA) injection resulted in failed mapping in 23/99 (23%) and aberrant drainage in 25/85 (29%). By comparison, peritumoral (PT) injection had a 14/38 (37%) incidence of failed mapping and 7/37 (19%) aberrant drainage (P = .11 and .23, respectively). Of the patients with successful sentinel lymph node (SLN) biopsy procedure via PA injection, 11/76 (14%) were positive for metastatic disease as compared with 2/24 (8%) in PT injection. Sixteen patients had lymph node metastases; 13 (81%) were SLNs, including 3 positive aberrant SLNs. Five-year regional recurrence rates were 11.4% (95% confidence interval, 0%-21.5%) and 0% for PA and PT injection techniques, respectively. ConclusionPA and PT injections had a similar incidence of SLN identification and aberrant drainage. Preoperative lymphoscintigraphy is beneficial in patients with recurrent breast cancer given the higher incidence of aberrant drainage in this population. Patients who underwent PA injections had a higher incidence of regional recurrences but this difference was not statistically significant.

Abstract PS14-09: The impact of non-classic LCIS on the natural history of DCIS

Abstract Background: Classic lobular carcinoma in situ (C-LCIS) and non-classic LCIS (NC-LCIS) are histologically and biologically distinct types of lobular neoplasia. Little is known about the impact of NC-LCIS on risk of recurrence when found in association with concomitant malignancy. We sought to assess oncologic outcomes in patients with DCIS and concomitant NC-LCIS as compared to DCIS with concomitant C-LCIS treated with breast conservation. Methods: Upon IRB approval, an institutional database was accessed to identify patients with a diagnosis of C-LCIS + DCIS or NC-LCIS+DCIS in the same core biopsy and/or excisional biopsy specimen. All pathology slides relevant to the diagnosis were confirmed by internal review. Patients with prior or concurrent ipsilateral invasive breast cancer and/or prior ipsilateral DCIS were excluded. Use of adjuvant therapies and the incidence of ipsilateral and contralateral DCIS and invasive breast cancer were compared in the 2 groups. Statistical analysis was performed using the chi-square test. Results: Among patients diagnosed with DCIS between 1996 and 2015 and treated with breast conserving surgery, 69 also had C-LCIS and 13 also had NC-LCIS (the diagnosis of NC-LCIS was not encountered until 2000). Median patient age was 55 years (range 40-88), 42 (51%) had a family history of breast cancer and 5 (6%) had a prior diagnosis of atypical proliferative breast lesions; these factors did not differ between patients with C-LCIS+DCIS and NC-LCIS+DCIS. Patients with NC-LCIS+DCIS were more likely to present with mammographic distortion (25% vs 6%, p=0.03), to have been diagnosed by core biopsy, and less likely to have ER positive (67% vs 91%, p=0.03) or PR positive (50% vs78%, p=0.014) DCIS. In 78% of the patient cohort, final excision margins were negative, and these proportions were not different between the 2 groups The median number of surgeries performed to obtain clear surgical margins which was 2 (range 1-4) for the entire cohort and for C-LCIS+DCIS and NC-LCIS+DCIS, individually. 78.% of C-LCIS+DCIS patients and 54% of NC-LCIS+DCIS patients received adjuvant radiation (p=0.064), and 45% of C-LCIS+DCIS patients took adjuvant hormonal therapy, while none of the NC-LCIS+DCIS patients did (p=0.002). At median follow-up of 78 (1-260) months for C-LCIS+DCIS and 60 (1-197) months for NC-LCIS+DCIS, there were no differences observed in the incidence of ipsilateral and contralateral breast cancer (10.1% vs 7.7% , p=0.19, and 10.1% vs 0%, respectively, p=0.78). One of 13 patients (7.7%) with NC-LCIS+DCIS, who developed an ipsilateral invasive carcinoma, was subsequently diagnosed with bone metastasis. Conclusions: Patients with NC-LCIS+DCIS were more likely to have ER and/or PR negative DCIS and only 54% of this cohort received radiation, yet local-regional recurrence rates were low and not different between NC-LCIS +DCIS and C-LCIS+DCIS patients. Despite the more aggressive histologic features of NC-LCIS, these data do not suggest that NC-LCIS associated with DCIS portends a different prognosis that C-LCIS associated with DCIS. Larger studies are needed to confirm these findings. Citation Format: Faina Nakhlis, Fisher Katlin, Samantha Grossmith, Ashley DiPasquale, Beth Harrison, Tari King. The impact of non-classic LCIS on the natural history of DCIS [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-09.

Abstract OT-08-02: Comparing an operation to monitoring, with or without endocrine therapy (COMET): A prospective randomized trial for low-risk DCIS (AFT-25)

Abstract Background: Approximately 50,000 women in the U.S. are diagnosed with ductal carcinoma in situ (DCIS) annually. Without treatment, it is estimated that 20-30% of DCIS will lead to invasive breast cancer. Currently, more than 97% of women undergo surgery, with many also undergoing radiation. An alternative to surgery for low-risk DCIS is active monitoring (AM), an approach in which regularly scheduled mammography and physical exams are used to monitor breast changes and determine if, or when, surgery is needed. Trial design: COMET, a multicenter phase III prospective randomized trial, opened in the U.S. in June 2017 (clinicaltrials.gov reference: NCT02926911). The hypothesis is that management of low-risk DCIS using an AM approach does not yield inferior invasive breast cancer and/or quality of life outcomes compared to surgery. Eligibility criteria: Patients with a new diagnosis of unilateral, bilateral, unifocal, multifocal, or multicentric DCIS, or atypia verging on DCIS are eligible. Patients must be ≥40 years of age, have no contraindication for surgery, and pathologic confirmation of grade I/II DCIS. DCIS must be ER and/or PR≥ 10% and HER2-negative without invasion, diagnosed within 120 days of registration. Breast tissue, blood and imaging are collected at trial entry and if invasive cancer subsequently occurs, and are stored in central repositories. Specific aims: The primary aim is to assess whether the 2-yr ipsilateral invasive breast cancer rate for AM is non-inferior to surgery. Secondary aims include comparison of 2-, 5-, and 10-yr mastectomy rate, contralateral invasive breast cancer rate, overall survival and invasive breast cancer-specific survival, as well as 5- and 10-yr ipsilateral invasive breast cancer rate between groups. Patient reported outcomes (PRO) using validated tools are critical secondary endpoints, and will enable comparison of health-related quality of life and psychosocial outcomes between surgery and AM groups at prespecified time points over a period of 5 years. Statistical methods: An accrual goal of 1200 was estimated using a 2-group test of noninferiority of proportions, with the 2-yr invasive breast cancer rate in the surgery group assumed to be 0.10, including accounting for upstaging. The projected drop-out rate is 25%, for a total of 900 patients treated per allocation arm. The non-inferiority boundary was set at 0.05. Based on a 1-sided un-pooled z-test, with alpha=0.05, a sample size of n=446 per group will have 80% power to detect the specified noninferiority margin. Intention-to-treat analysis of the 2-yr invasive breast cancer rate will be conducted using all patients as randomized, and will be completed using Kaplan-Meier estimates, stratified by group, combined with Greenwood’s confidence interval. Several sensitivity analyses (per protocol, as-treated, and instrumental variable) are also planned to account for loss of follow-up, rejection of randomization allocation and withdrawals. Present and target accrual: Trial accrual as of 7/1/20 is 540 randomized patients from 84 activated Alliance for Clinical Trials in Oncology sites. Despite logistical challenges posed by the COVID-19 crisis, patients continue to be recruited to the COMET trial. Over 80% of patients have sample sets/images stored in the tissue and image repositories. This trial will provide definitive clinical, quality of life and biomarker evidence regarding the trade-offs of surgery vs AM in patients with low-risk DCIS. Support: CER-1503-29572; https://acknowledgments.alliancefound.org Contact: Thomas Lynch (Project Manager) - thomas.lynch2@duke.edu Citation Format: Thomas Lynch, Ann Partridge, Alastair Thompson, Elizabeth Frank, Donna Pinto, Deborah Collyar, Desiree Basila, Louise Davies, Jenny Donovan, Terry Hyslop, Linda McCall, Marc Ryser, Taylor O' Donnell, Anna Weiss, Shelley Hwang. Comparing an operation to monitoring, with or without endocrine therapy (COMET): A prospective randomized trial for low-risk DCIS (AFT-25) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-08-02.