Selected Breast Cancer Patients Research Articles

Minimally Invasive Mastectomy Could Achieve Non-inferior Oncological Outcome in Appropriately Selected Patients: Propensity Matched Analysis of the National Cancer Database.

Minimally invasive mastectomy (MIM) was emerged as an approach to decrease morbidity and increase patient satisfaction through improved cosmetic results; however, there is a paucity of data regarding the long-term oncologic outcomes of these minimally invasive approaches. Patients who underwent mastectomy procedures were identified in the National Cancer Database (2010-2016). Patients were categorized as MIM or open mastectomy. A 1:1 propensity match was performed to balance the bias on reconstruction, nipple sparing, lymph node procedures, and other confounding factors between the cohorts. Short- and long-term outcomes were compared. A total of 328811 patients met the criteria: 327643 (99.6%) received open mastectomy and 1168 (.4%) received MIM. Propensity match identified 384 "pairs" of MIM and open mastectomy patients. Among them, MIM was associated with shorter length of stay (LOS) (mean 1.3 vs. 1.06 days, P = .003). No differences were observed in the rates of positive margins, unplanned readmissions, or 90-day mortality between the 2 operative approaches. Overall survival (OS) was equivalent between MIM and open mastectomy patients. Cox proportional hazard regression showed no effect of the procedure performed on OS. MIM is associated with shorter LOS, and it is non-inferior to open mastectomy in terms of other short-term outcomes and long-term oncologic survival outcomes. These data suggest that MIM may be considered in appropriately selected breast cancer patients as an additional approach to the community.

Abstract OT-19-01: Phase I study to evaluate the safety and feasibility of preoperative ablative radiotherapy (SABER) for selected early stage breast cancer

Abstract Background: Breast conserving therapy is an established option for early stage breast cancer. Shorter postoperative radiotherapy (RT) regimens have similar efficacy in lower risk breast cancer, including hypofractionated whole breast RT and Accelerated Partial Breast Irradiation (APBI). Despite similar efficacy results for APBI, RAPID trial showed worse cosmetic outcomes for patients receiving APBI compared to whole breast RT. Larger postoperative lumpectomy cavity volumes and the used dose regimen could have had an impact on cosmesis. There are only few published preoperative APBI pilot studies with different dosimetric schemes treating smaller RT target volumes that would potentially translate into less toxicity. Our study is designed to evaluate the safety and feasibility of preoperative ablative RT in patients with early stage breast cancer. An array of ancillary imaging, blood and tissue biomarker collection is also planned in order to study the radiation response in breast cancer. Trial Design: This phase I study uses a modification of the standard 3+3 Phase I design to identify the recommended phase 2 dose of preoperative SABER for treatment of selected breast cancer patients. Participants will be treated with assigned dose level of preoperative SABER, once a day, for 5 fractions given on non-consecutive days, over a period of 2 weeks. The tested dose levels are: Level I=35 Gy (7 Gy x 5), Level II (starting dose)= 40 Gy (8 Gy x 5), Level III=45 Gy (9 Gy x 5), Level IV=50 Gy (10 Gy x 5). Standard partial mastectomy and axillary surgery will be performed 4-6 weeks after preoperative SABER. Adjuvant systemic therapy will be per standard of care. Exploratory studies will be performed pre/post RT and postoperative, including multiparametric breast MRI, biomarkers in blood (CTC’s, SNPs, cytokines, CRP) and tissue (assessment of radiation response, expression of PD-L1, PD1, TILs). Cosmesis and QoL assessment will be performed at scheduled 1, 6, 12, 24 months follow-up. Eligibility criteria: Women, 50 or older, clinical stage T1 unifocal, N0, ER/PR+/HER2 negative, ECOG 0-1, able to undergo MRI with contrast are eligible. Specific Aims: Aim 1. To identify the recommended phase II dose of preoperative SABER; Aims 2.a) to determine the safety, tolerability, Dose Limiting Toxicity (DLT) and toxicity profile of delivering SABER; b) to determine the rate of complete pathological response after preoperative SABER; c) To assess cosmetic results (by MD and patient’s assessment) and QoL after SABER and standard partial mastectomy/axillary surgery. Exploratory aims: a) to determine biomarkers in blood and tissue, and multiparametric MRI radiographic changes and associate them with toxicity and radiation tumor response; b) to assess locoregional recurrence, disease-free survival, and overall survival; c) to assess sentinel lymph node biopsy identification rates after SABER. Statistical Methods: In this novel phase I study, escalation to the next higher dose level will occur only if 0 or only 1 out of 6 patients has DLT. Present accrual and target accrual: A total of 12 to 18 evaluable patients will be enrolled. Expected enrollment period is 3 years and time to complete the study is about 5 years. Open for accrual in 06/2020. Clinical trial information: NCT04360330 Citation Format: Cristiane Takita, Isildinha M. Reis, Radka Stoyanova, John C. Ford, Brian Marples, Jose Net, Monica Yepes, Carmen Gomez, Susan Kesmodel. Phase I study to evaluate the safety and feasibility of preoperative ablative radiotherapy (SABER) for selected early stage breast cancer [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-19-01.

Efficacy of PARP inhibition combined with EZH2 inhibition depends on BRCA mutation status and microenvironment in breast cancer.

The efficacy of the combination of a PARP inhibitor (PARPi) and an EZH2 inhibitor has been investigated in breast cancer cells with either BRCA1 mutation or BRCA2 mutation. However, earlier studies focused on the efficacy of this combination against BRCA-mutated but not BRCA-proficient breast cancer. Yang et al. observed that PARP1 depletion combined with EZH2 depletion via PRC2 depletion did not affect the growth of BRCA1/2 wild-type breast cancer cells invitro. Moreover, Yang et al. reported that this combination stimulated synthetic viability of BRCA1/2-proficient breast cancer cells invivo by regulating the tumor microenvironment to induce angiogenesis and differentiation of M2-type macrophages. The findings of Yang et al. provided evidence that both invitro and animal models should be employed in the studies of PARPi combination therapies in order to involve the alteration of the tumor microenvironment in these investigations. These studies of PARP inhibition combined with EZH2 inhibition in breast cancer showed that this combination may benefit breast cancer patients carrying BRCA1-mutated tumor, but the combination may also enhance recurrence of BRCA2-mutated tumor and may even promote BRCA-proficient cancer cell survival. Therefore, BRCA1 mutation status should be used to select breast cancer patients for PARPi and EZH2 inhibitor combination treatment in clinical trials in the future.

Impact of ARTs on oncological outcomes in young breast cancer survivors.

Impact of ARTs on oncological outcomes in young breast cancer survivors.

Identification of breast cancer patients with pathologic complete response in the breast after neoadjuvant systemic treatment by an intelligent vacuum-assisted biopsy.

Neoadjuvant systemic treatment elicits a pathologic complete response (pCR) in about 35% of women with breast cancer. In such cases, breast surgery may be considered overtreatment. We evaluated multivariate algorithms using patient, tumor, and vacuum-assisted biopsy (VAB) variables to identify patients with breast pCR. We developed and tested four multivariate algorithms: a logistic regression with elastic net penalty, an Extreme Gradient Boosting (XGBoost) tree, Support Vector Machines (SVM), and neural network. We used data from 457 women, randomly partitioned into training and test set (2:1), enrolled in three trials with stage 1-3 breast cancer, undergoing VAB before surgery. False-negative rate (FNR) and specificity were the main outcome measures. The best performing algorithm was validated in an independent fourth trial. In the test set (n=152), the logistic regression with elastic net penalty, XGboost tree, SVM, and neural network revealed an FNR of 1.2% (1 of 85 patients with missed residual cancer). Specificity of the logistic regression with elastic net penalty was 52.2% (35 of 67 women with surgically confirmed breast pCR identified), of the XGBoost tree 55.2% (37 of 67), of SVM 62.7% (42 of 67), and of the neural network 67.2% (45 of 67). External validation (n=50) of the neural network showed an FNR of 0% (0 of 27) and a specificity of 65.2% (15 of 23). Area under the ROC curve for the neural network was 0.97 (95% CI, 0.94-1.00). A multivariate algorithm can accurately select breast cancer patients without residual cancer after neoadjuvant treatment.

Intraoperative Radiation Therapy for Early-Stage Breast Cancer: A Single-Institution Experience

We assessed patient outcomes and toxicity after the use of intraoperative low-energy photon radiotherapy for select early-stage breast cancer (ESBC) patients. This is a retrospective review of patients with unilateral ESBC treated with breast-conservation surgery followed by low-energy photon intraoperative radiotherapy (IORT) at a single institution between 2010 and 2017. Institutional suitability guidelines included: age ≥ 50 years, invasive ductal carcinoma (IDC) with or without DCIS, grade 1 – 2 tumors < 3 cm, ER and or PR positive, Her2 negative, clinically node negative, no lymphovascular space invasion (LVSI), and negative margins (>2 mm). 20 Gy was prescribed to the surface of the spherical applicator fitted to the surgical cavity at surgery. Postoperative patients who did not meet institutional guidelines for IORT alone were recommended adjuvant treatment, including possible additional surgery, external-beam radiotherapy (EBRT), chemotherapy, and/or endocrine therapy. Kaplan-Meier estimates and Cox regression analysis were used to assess ipsilateral breast tumor recurrence (IBTR), overall survival (OS), and relapse-free survival (RFS). 201 patients were included with a median follow up of 5.1 years. Most patients met institutional guidelines for IORT for ESBC. The median age was 67 years; 88% were Her2 negative and ER positive and/or PR positive, 97% had IDC, 87% had grade 1 or 2 disease on biopsy, and 95% had T1 disease. On final pathology, 8% had LVSI, 25% had close (<2 mm) margins, and 3% had positive margins. Most had pathological T1 (93%) N0 (95%) disease. The median IORT applicator size was 4.5 cm with a mean dose at 1 cm depth of 6.3 Gy delivered over an average of 37 minutes. 10% of patients completed additional surgery, 11% additional EBRT, 9% adjuvant chemotherapy, and 74% received adjuvant hormonal therapy. The median total EBRT dose was 42.4 Gy (range 40.05 - 63 Gy) with a median dose of 2.65 Gy/fraction. The 5-year cumulative risk of IBTR was 2%. There was no statistically significant difference in IBTR between patients considered unsuitable by our institutional guidelines (p = 0.93) or by the 2016 ASTRO consensus guidelines (p = 0.26) compared to patients who were considered suitable for IORT alone, by respective guidelines. Of the 98 patients who did not meet institutional criteria based on final surgical pathology, 32% received adjuvant EBRT. Of the 9 patients who experienced IBTR, 5 patients did not undergo indicated EBRT. The 5-year OS rate was 95% with no breast cancer-related deaths. The 5-year RFS rate was 96%. 83% of patients had documented toxicity information and the overall highest reported grade 3 toxicity was 8%; seroma was the most common grade 3 toxicity (4%). IORT for select patients with ESBC has led to acceptable outcomes in regards to ipsilateral breast tumor recurrence and toxicity. We continue to recommend adjuvant EBRT for patients who do not meet IORT suitability criteria upon review of final pathology.

201P 70-gene signature to select breast cancer patients for neoadjuvant endocrine treatment

201P 70-gene signature to select breast cancer patients for neoadjuvant endocrine treatment

Abstract 2315: Perceived barriers to early diagnosis of breast cancer in south and southwestern Ethiopia: Qualitative study

Abstract Background: Early diagnosis is a key determinant of breast cancer prognosis and survival. However, advanced stage presentation and delays in diagnosis are common problems in Ethiopia. More than half of the cases are diagnosed at advanced stages and the barriers to early diagnosis are not well studied in the country. Hence, this study aims to explore perceived barriers to early diagnosis of breast cancer in South and Southwestern Ethiopia. Methods: A qualitative study was conducted from March to April 2018 in six selected public hospitals located both in urban and rural settings. Twenty five purposefully selected breast cancer patients and health care providers from these public hospitals were interviewed. An in-depth interview was conducted using a topic guide by qualitative research experts. A thematic analysis was performed using Open Code software version 4.02. Results: Patient and health system related barriers are two main themes identified for barriers to early diagnosis of breast cancer. Patient related barriers included lack of awareness and knowledge of the disease, beliefs in traditional and religious means of treatments, lack of social and financial support to seek medical care. Health system related barriers included misdiagnosis of cases, long distance referrals due to service inaccessibility, high diagnostic costs, long waiting time, unavailability of screening and diagnostic tests. Conclusion: Early diagnosis of breast cancer is affected by a multitude of barriers in South and Southwestern Ethiopia. Hence, to increase early diagnosis of breast cancer, awareness campaigns and education about the disease, its prevention, and early detection are needed. Opportunities exist to improve early diagnosis and timely treatment by strengthening referral linkages of health care facilities in rural areas. Efforts are needed to decentralize the tertiary level oncology care and improve capacity in local health facilities. Citation Format: Sefonias Getachew, Adamu Addissie, Aragaw Tesfaw, Lesley Taylor, Eva Kantelhardt. Perceived barriers to early diagnosis of breast cancer in south and southwestern Ethiopia: Qualitative study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2315.

Quality-of-Life and Surgical Outcomes for Breast Cancer Patients Treated with Therapeutic Reduction Mammoplasty Versus Mastectomy with Immediate Reconstruction.

Therapeutic reduction mammoplasty (TRM) is a safe and effective surgical technique that has oncologic outcomes comparable with those achieved by mastectomy. This study aimed to compare surgical and patient-reported outcomes between breast cancer patients treated with TRM and those who had mastectomy with immediate reconstruction (MIR). A 4-year, single-institution, retrospective cohort study analyzed breast cancer patients undergoing TRM and MIR. Patient characteristics and perioperative data were collected from electronic records. Patient-reported outcome data were collected via BREAST-Q questionnaires preoperatively, then 3months and 12months postoperatively. A subgroup analysis was performed on locally advanced breast cancer (LABC) patients for TRM and MIR. The study included 249 breast reconstructions, of which 77 (31%) were TRM and 172 (69%) were MIR. The mean follow-up time was 2.4 ± 1.2years. Compared with MIR, TRM had significantly lower major complication rates (9% vs 21%; p = 0.02) and fewer revisionary surgeries (5% vs 37%; p < 0.0001). At 1year postoperatively, TRM had a significantly greater change in satisfaction with breasts, (+ 27.7 vs + 4.6; p < 0.01) and sexual well-being (+ 20.0 vs - 5.5; p = 0.02) than MIR. For select breast cancer patients, TRM continues to be a safe and effective alternative to mastectomy. The current study demonstrated that TRM patients had fewer major complications and revisionary surgeries, as well as better patient-reported outcomes than MIR.

Role of Bone Targeting Agents in the Prevention of Bone Metastases from Breast Cancer.

Breast cancer (BC) is the most common malignancy in women worldwide and leads, in more than 70% of patients with advanced disease, to skeleton colonization and formation of bone metastases (BM). This condition implies a severe disability and deterioration of the quality of life, with consequent additional social costs. In recent decades, several studies explored the role of agents acting within the bone microenvironment to counteract BM development, and several bone-targeting agents (BTAs) have been introduced in the clinical practice to manage bone lesions and reduce the risk of skeletal complications. However, long-term exposure to these agents is not free from potential toxicities and needs careful monitoring. In this context, the potential capability to prevent BM onset in selected BC patients, through the early administration of BTAs, has been explored by several researchers, with the belief that “prevention is better than cure” and that, ultimately, metastatic BC is an incurable condition. Here, we revised the mechanisms of BM development in BC as well as the strategies for selecting high-risk patients suitable for early BTA treatment.

The actual benefit of intraoperative radiation therapy using 50kV x-rays in early breast cancer: A retrospective study of 676 patients.

This French study reports the 5-year results of partial-breast irradiation using intraoperative radiation therapy (IORT) with 50kV x-rays, in select early breast cancer patients. We report a retrospective analysis of 676 consecutive early breast cancer patients treated between November 2011 and December 2015 by partial-breast irradiation using the INTRABEAM® system. Patients were highly selected based on the ASTRO and GEC-ESTRO criteria and underwent breast-conservative surgery and IORT, completed with additional whole-breast irradiation (WBI) when unexpected unfavorable prognostic factors were found at the final pathology report. Patients' outcomes relative to local and distant control, overall and breast cancer-specific survival, and toxicity are presented, as well as rates of additional WBI. Additional WBI was mandatory in one third of patients (31%), mainly due to lymph node involvement and extensive intraductal component. With a median follow-up time of 54months, the 5-year local recurrence rate was 1.7% [95%CI: 0.9-3.3]; the median time to local recurrence was 23months; ipsilateral breast recurrences mainly occurred in the same quadrant (7/11); in the restricted population, meeting all predefined criteria and treated with IORT alone (406 patients), the local recurrence rate was 1.5% [95%CI: 0.6-3.6]. Five-year distant tumor control was 98.6% [95%CI: 97.2-99.3], and the median time to distant recurrence was 22months. Five-year overall survival was 96.5% [95%CI: 94.2-97.8], and 5-year breast cancer-specific survival was 98.9% [95%CI: 97.6-99.7]. In patients treated with IORT alone, there was no grade 3 toxicity, only four grade 3 (mainly fibrosis) affected patients treated with IORT and WBI. Grade 1-2 toxicity rates were 14% and 34.4% in patients treated with IORT alone and IORT plus WBI, respectively. Partial-breast irradiation using IORT by a 50 kV photon device is safe and well-tolerated in select patients with early breast cancer and is a valuable option in patients reluctant for adjuvant WBI.

Comparison between 18F-FDG and 18F-NaF PET imaging for assessing bone metastases in breast cancer patients: a literature review

In patient with breast cancer (BC), 18F-FDG PET/CT is widely used for assessing skeletal metastatic involvement. Also 18F-NaF PET imaging is considered an accurate modality for detecting bone metastases. We aimed to review current literature on comparative performances of 18F-FDG and 18F-NaF PET imaging for assessing bone metastases from BC. A literature search for PET studies published in PubMed/MEDLINE database in the last 10 years (September 2009–September 2019) using both 18F-FDG and 18F-NaF to detect bone involvement in BC patients was conducted, based on the combination of the terms (“PET” OR “positron emission tomography”) AND ((“FDG” OR “fluorodeoxyglucose” AND “fluoride” OR “NaF”)) AND “breast cancer”. Data on clinical and methodological aspects and diagnostic performances between the two tracers were collected and compared. Out of 43 studies initially retrieved, 12 studies (overall 340 patients) were finally considered, 3/12 performing a combined 18F-FDG/18F-NaF (“cocktail”) imaging. Heterogeneity in several aspects has been found among studies. However, 18F-NaF PET demonstrated overall higher sensitivity than 18F-FDG (ranging from 91.7 to 100% and from 41.6 to 75%, respectively), potentially impacting on patients’ management, but with lower specificity due to non-tumor-specific bone uptake (ranging from 46.3 to 76.2% and from 94.3 to 99%, respectively). 18F-FDG only is able to detect early metastases confined to bone marrow. Occurrence of “flare phenomenon” limits the use of 18F-NaF for assessing early treatment response. Cocktail imaging may allow the most comprehensive evaluation of bone involvement, moreover with dosimetry advantages over two single-tracer PET scans, but losing prognostic information carried by 18F-FDG. Both 18F-NaF and 18F-FDG are suitable for assessing skeletal involvement in BC patients. However, inherent different uptake mechanism highlights differences in diagnostic performance between these tracers, reflecting specific bone metastases’ characteristics. Therefore, a complementary use of 18F-NaF and 18F-FDG PET imaging may be considered in clinically selected BC patients, such as those with suspicious bone involvement despite negative 18F-FDG PET imaging, with prevalent CT-sclerotic bone findings or with apparently confined or oligo-metastatic cancer to exclude widespread disease.

Oncologic Outcomes of Nipple-sparing Mastectomy and Immediate Reconstruction After Neoadjuvant Chemotherapy for Breast Cancer.

To evaluate the oncologic outcomes and risk factors for locoregional recurrence (LRR) and nipple-areola complex recurrence (NR) in a large series of breast cancer patients who underwent nipple-sparing mastectomy (NSM) and immediate reconstruction after neoadjuvant chemotherapy (NACT). The use of NSM and immediate reconstruction in breast cancer patients receiving NACT is increasing. However, the oncologic safety of this approach is unclear. A total of 310 breast cancer patients (319 breasts) who underwent NACT and NSM between February 2010 and November 2016 were retrospectively analyzed. Clinical and pathologic factors associated with increased risks of LRR and NR were analyzed using univariate (Chi-square or Fisher exact test) and multivariate (Cox proportional hazard regression model) analyses. During a mean follow-up of 63 ± 22 months, 38 cases had LRR as the first event, including 6 cases of NR as the first event. The 5-year cumulative LRR and NR rates were 11.0% and 1.9%, respectively. In univariate analysis, clinical T stage, pathologic nodal status, histologic grade, lymphovascular invasion, and post-NACT Ki67 status were associated with increased LRR risk, and post-NACT Ki67 status was the only significant risk factor for NR. In multivariate analysis, post-NACT Ki67 ≥10% (hazard ratio, 4.245; 95% confidence interval, 1.865-9.663; P = 0.001) was an independent risk factor for LRR. NSM and immediate reconstruction seem to be oncologically safe with acceptable LRR and NR rates for appropriately selected breast cancer patients treated with NACT. Post-NACT Ki67 ≥10% was associated with increased risk of LRR or NR, and therefore, necessitates cautious follow-up.

Abstract P4-12-16: A seven year single institution experience with IntrabeamTM intraoperative radiation therapy:recurrence rates and predictors of recurrence

Abstract Objectives: Patients undergoing single fraction intraoperative radiation therapy (IORT) for early stage breast cancer were analyzed to determine rates of local recurrence and to identify predictors of local recurrence. Materials and Methods: Patients who underwent intraoperative radiotherapy (IORT 20 Gray at 50kV using the INTRABEAMTM IORT system) have been analyzed over a 7 year period. The procedures were performed at a single institution by a single surgical and radiation oncology group. Post-operative whole breast radiotherapy (WBRT) was generally recommended in high risk patients with positive sentinel lymph nodes (SLN), lymphovascular invasion (LVI), extensive intraductal component (EIC), or positive margins requiring re-excision. Local recurrence was defined as any same breast recurrence during the follow-up period. Results: A total of 438 patients were included in the analysis. Median follow-up was 35 months. Median age was 68 years, mean tumor size on preoperative ultrasound was 1.2 cm. Patient characteristics are listed below: Patient/Tumor CharacteristicnGrade 1-232474.5%Grade 311125.5%Presence of LVI429.9%Presence of EIC4811.6%ER Negative429.7%PR Negative7918.4%DCIS only6514.4%Invasive Lobular only102.2%Positive SLN276.9%Re-excision performed6013.7% A total of 16 patients (3.7%) had a local or simultaneous local/regional recurrence. Median time to recurrence was 24.5 months. When analyzing associations between predictor variables and local recurrence using logistic regression, it was found that high tumor grade, EIC, LVI, DCIS or DCIS component, and need for re-excision were significant (p&amp;lt;0.05) predictors of local recurrence. Furthermore, there was a strong association with local recurrence and time to local recurrence when adjuvant endocrine therapy was recommended but the patient was either non-compliant or discontinued use due to side-effects (odds ratio 0.064, p&amp;lt;0.0005). Conclusions: INTRABEAMTM IORT can be used in select breast cancer patients with low local recurrence rates. Unfavorable tumor features and non-compliance with adjuvant endocrine therapy result in the highest risk of local recurrence. Better patient selection and pre-treatment education should minimize this risk. Citation Format: Christina Munford, William E Burak Jr, Krista Miller, Jennifer Davis, Nicole Neal, Caleb Price, Matthew Bertke, Michael Hasselle, Aaron Pederson. A seven year single institution experience with IntrabeamTM intraoperative radiation therapy:recurrence rates and predictors of recurrence [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-16.

Surgery of the Primary Tumor Offers Survival Benefits of Breast Cancer with Synchronous Ipsilateral Supraclavicular Lymph Node Metastasis

BackgroundControversy exists around the locoregional management of the primary tumor for breast cancer associated with synchronous ipsilateral supraclavicular lymph node metastasis (sISLM) due to the rarity of the disease and limited available data. This study aimed to compare outcomes of patients in the Surveillance, Epidemiology, and End Results (SEER) database with sISLM who underwent surgical resection and radiation of the primary tumor with those who did not.MethodsThis population-based retrospective study included breast cancer patients with sISLM without distant metastases from 2004 to 2016 in the SEER database. In this study, patients had been stratified by operative management, and propensity score matching (PSM) had been successfully applied.ResultsA total of 1172 breast cancer patients with sISLM were included in the study: 863 (73.6%) of patients underwent the primary tumor resection, and 309 (26.4%) patients did not undergo surgery. The median survival time in the surgery group was longer compared to the nonsurgery group in the overall cohort and the PSM cohort. We concluded that the primary tumor resection was associated with improved survival. Subgroup analysis further demonstrated that local surgery was not inferior to radical surgery.ConclusionFor selected breast cancer patients with sISLM, surgery is a promising local intervention which may improve the survival.

Is axillary lymph node dissection necessary for positive preoperative aspiration cytology lymph node results?

IntroductionBased on international guidelines, axillary lymph node dissection (ALND) is recommended in cases of breast cancer if preoperative examinations confirm axillary metastasis. We examined which set of preoperative parameters might render ALND unnecessary. Patients and methodsPreoperative examinations (axillary ultrasound and aspiration cytology) confirmed axillary metastasis in 190 cases out of 2671 patients with breast cancer; primary ALN dissection was performed on these patients with or without prior neoadjuvant therapy. The clinicopathological results were analysed to determine which parameter might predict the presence of no more than 2 or 3 metastatic ALNs. ResultsThe final histological examination confirmed 1–3 metastatic lymph nodes in ALND samples in 116 cases and over 3 metastatic lymph nodes in 74 cases.For patients receiving neoadjuvant therapy (59 out of the 190 cases), if the size of the primary tumour was 2 cm or smaller and/or the metastatic ALN was 15 mm or smaller, then the patient was likely to have no more than 3 positive ALNs (stage N0–1 disease) (p < 0.001). If the patient did not receive neoadjuvant therapy, stage N2 or N3 disease was very likely. No correlation was found between other clinicopathological characteristics of the tumour and involvement of the ALNs. ConclusionAxillary lymph node dissection is not necessary for selected breast cancer patients with axillary metastasis receiving neoadjuvant therapy. In these cases, sentinel lymph node biopsy with or without radiation therapy and close follow-up may serve as adequate therapy.

Efficacy, late complications, and cosmetic outcomes of targeted intraoperative radiotherapy in breast-conserving surgery for early-stage breast cancer: a single-centre study in China.

The purpose of this study was to evaluate the efficacy, late complications, and cosmetic outcomes of targeted intraoperative radiotherapy for the treatment of Chinese patients with early-stage breast cancer. Between September 2014 and May 2017, breast cancer patients undergoing targeted intraoperative radiotherapy at our facility were retrospectively recruited for this study. Intraoperative radiotherapy was performed with a 50-kV X-ray source in an Intrabeam system (Carl Zeiss Meditec, Oberkochen, Germany). The one-time prescribed irradiation dose to the tumour bed was 20Gy. Recurrence, death, late complications, and cosmetic outcomes were recorded. Late radiotoxicity was assessed based on the grading criteria of the Radiation Therapy Oncology Group. A total of 77 patients who were treated with targeted intraoperative radiotherapy only were recruited. The cohort had a mean age of 58years; patients with T1, N0, and invasive ductal carcinoma accounted for 75.3, 89.6, and 84.4%, respectively; the median follow-up duration was 40months; there were 2 patients of recurrence and 2 patients of death. There were no patients of cardiac toxicity or skin or lung radiotoxicity of grade 2 or above. The main complications were breast oedema (18.2%), seroma (15.6%), chromatosis (9.1%), induration (7.8%), pain (5.2%), skin depression (2.6%), mild dry cough (2.6%), delayed wound healing (1.3%), and wound infection (1.3%). Seventy-three patients participated in the cosmetic outcome evaluation, which yielded an excellent or good rate of 95.9%. Due to its low recurrence rates, lack of high-grade late radiotoxicity, and excellent cosmetic outcomes, targeted intraoperative radiotherapy may be a suitable treatment for select early-stage breast cancer patients in China.

Robotic Stereotactic Accelerated Partial-Breast Irradiation for Early-Stage Breast Cancer: 5-Year Results of a Single-Institution Pilot Study

Outcomes following adjuvant accelerated partial breast irradiation (APBI) in select women with early stage breast cancer are comparable to whole breast irradiation. Robotic stereotactic accelerated partial breast irradiation (SAPBI) with fiducial tracking is an attractive treatment option, but limited data are available regarding the feasibility of this approach and 5 year outcomes have not yet been published. We report our institutional experience treating select women with SAPBI. Women with DCIS and early stage breast cancer treated from November 2008 to September 2015 were evaluated. Treatments were delivered with a robotic radiosurgical system. At least 4 gold fiducials were implanted around the lumpectomy cavity prior to the start of treatment for target tracking. The CTV was delineated on contrast enhanced CT scans using surgical clips and the lumpectomy cavity. In 2014, following the publication of the University of Florence phase III trial, the protocol was amended after 13 patients and the CTV was defined as the lumpectomy cavity with a uniform 1 cm expansion confined to the breast tissue. The PTV, prescribed 30 Gy in 5 fractions, was defined as the CTV with a 3-5 mm uniform expansion. AAPM TG-101 skin dose constraints were respected. Clinical examination and mammography were completed at 6-12 month follow up intervals. Breast cosmesis was scored using The Harvard Breast Cosmesis Grading Scale. Twenty women (median age 65 years) were treated over a median 7 days (range 5-13). Fourteen women had DCIS and 50% of the tumors were located in the upper outer quadrant. The median treated PTV was 63 cm3 (range 15-142), the median PTV/breast volume ratio was 8.3% (range 4.1-25.6) and the median prescription isodose line was 83% (range 75-87). Three or 4 fiducials were successfully tracked in 90% of patients. At a median follow up of 60 months (range 33-108), locoregional control, distant control, and overall survival was 100%. Five women with skin Dmax > 33 Gy (skin = CT surface minus 2 mm) developed chronic grade 1 dermatitis (faint hyperpigmentation), one of whom developed focal grade 1 telangiectasia at 52 months. Three women developed grade 1 fibrosis, one of whom was later diagnosed with fat necrosis on mammography. Two additional asymptomatic women were diagnosed with fat necrosis on routine mammography. There were no rib fractures. One woman required stereotactic biopsy to confirm benign tumor bed calcifications at 66 months. Fifteen evaluable patients maintained Good-Excellent cosmesis. Robotic SAPBI with fiducial tracking is a feasible, well tolerated and highly effective technique for the adjuvant treatment of select early-stage breast cancer patients. Cosmetic outcomes may be improved further by decreasing the skin Dmax to < 33 Gy. A confirmatory multi-institutional registry is actively enrolling patients. Given these encouraging results, future research in this patient population will evaluate robotic SAPBI as a definitive treatment.

Linac-Based Radiosurgery for Patients With Brain Oligometastases From a Breast Primary, in the Trastuzumab Era-Impact of Tumor Phenotype and Prescribed SRS Dose.

Background: The role of stereotactic radiosurgery (SRS) in the treatment of limited numbers of brain metastases in selected breast cancer patients is well-established.Aims: To analyse outcome from a single institutional experience with SRS, to identify any significant prognostic factors and to assess the influence of Her-2, estrogen receptor status, and prescribed dose on outcome.Methods: The medical records of 56 patients treated at in a single institution between 2009 and 2014 were reviewed. Demographic, treatment related and outcome data were analyzed to identify prognostic factors in this patient population. The primary endpoints were overall survival and local control. Secondary endpoint was distant intra-cranial progression-free survival.Results: The median follow- up time for the entire cohort was 10.33 months (1.25–97.28). The overall median survival was 12.5months (95%CI = 5.8–19.2), with 53.3%, and 35.8% surviving at 1- and 2- years post-SRS. After adjustment for the effect of Her 2 status, uncontrolled extra-cranial disease at the time of SRS predicted for shorter survival (HR for death = 3.1, 95% CI = 1.4–6.9, p = 0.006). At the time of death, 75% of the patients had active, uncontrolled intra-cranial disease, with 56% these patients presenting intra-cranial disease only. Sustained local control was observed in 56 (59.6%) of 94 treated metastases. In univariate analysis, Her2 status, ERHer2 group status?, and prescribed SRS dose were highly significant for local progression free-survival (LPFS). After adjustment for the effect of Her 2 status, patients receiving 12–16 Gy can expect shorter LPFS than those receiving 18–20 Gy (HR = 1.7, 95% CI = 1.0–2.8, p = 0.043). After adjustment for the effect of dose group, patients with Her 2 negative cancer can expect shorter LPFS than those with Her 2 positive cancer (HR = 2.6, 95% CI = 1.5–4.4, p < 0.0005). Use of prior WBRT did not impact survival, local or distant intra-cranial progression-free survival.Conclusions: Survival outcome is similar to the published literature. Improved outcomes are observed in patients with Her 2-positive, controlled extracranial disease at the time of SRS and higher SRS dose delivered. Achieving intra-cranial control appears to be an important factor for the survival of the breast cancer patients in the era of targeted therapies.

Optimal Selection of Breast Cancer Patients for Elimination of Surgery Following Neoadjuvant Systemic Therapy

Kuerer, Henry M. MD, PhD; Krishnamurthy, Savitri MD; Rauch, Gaiane M. MD, PhD; Yang, Wei T. MD; Smith, Benjamin D. MD; Valero, Vicente MD Author Information