5-year Ipsilateral Breast Tumor Recurrence Research Articles

Selective Avoidance of Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Human Epidermal Growth Factor 2-Positive/Triple-Negative Breast Cancer Patients With Excellent Response.

The Avoid Axillary Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy (ASLAN) trial aims to demonstrate the oncologic safety of omitting axillary surgery in patients with excellent response after neoadjuvant chemotherapy (NACT) for early human epidermal growth factor 2 (HER2)-positive (+)/triple-negative breast cancer (TNBC) who have undergone breast-conserving surgery (BCS) and adjuvant radiotherapy. The ASLAN trial will provide crucial information that could change the procedure in highly selected patients undergoing axillary surgery after NACT. ASLAN is a prospective, multicenter, and single-arm surgical trial. The recruitment will be conducted among five tertiary care hospitals in the Republic of Korea. The total number of patients to be recruited will be 178, and we plan to complete patient enrollment by December 2023. The enrollment is considered among patients with HER2+ breast cancer (BC) or TNBC at clinical stage T1-3N0-1M0 who are expected to achieve breast pathological complete response (BpCR) based on a combination of radiologic imaging and physical examination after NACT. BCS was performed on eligible patients. After BCS, patients who showed BpCR were enrolled with the omission of sentinel lymph node biopsy (SLNB). The primary study endpoint upon completion of this trial is 5-year recurrence-free survival, and the secondary endpoints include the 5-year ipsilateral breast tumor recurrence interval, 5-year ipsilateral axillary recurrence interval, 5-year distant metastasis-free survival, 5-year BC-specific survival, 5-year overall survival, 5-year contralateral BC-free survival, re-operation rate according to breast biopsy after NACT, adverse events within 5 years, and quality of life. Several clinical trials are currently underway to determine whether SLNB can be omitted after NACT in patients with HER2+ BC or TNBC that are expected to achieve pathologic complete response. The ASLAN trial is expected to provide valuable clues regarding the feasibility of omitting axillary surgery in highly selected patients. ClinicalTrials.gov Identifier: NCT04993625. Registered on August 6, 2021. Clinical Research Information Service Identifier: KCT0006371. Registered on July 22, 2021.

Preferences Regarding Breast Surgery Omission Among Patients With Breast Cancer Who Receive Neoadjuvant Chemotherapy.

Currently, several ongoing prospective studies are investigating the safety of breast surgery omission in patients with breast cancer who are exceptional responders to neoadjuvant chemotherapy. However, there is little information about the preferences of these patients regarding omission of breast surgery. We conducted a questionnaire survey to assess preferences regarding omission of breast surgery among patients with breast cancer who had human epidermal growth factor receptor 2-positive or estrogen receptor-negative tumors and good clinical response after neoadjuvant chemotherapy. Patients' estimation of the risk of ipsilateral breast tumor recurrence (IBTR) after definitive surgery or breast surgery omission was also assessed. Of 93 patients, only 22 (23.7%) said they would omit breast surgery. Under the scenario of omitting breast surgery, the 5-year IBTR rate estimated by patients who said they would omit breast surgery was significantly lower (median, 10%) than the rate estimated by patients who preferred undergoing definitive surgery (median, 30%) (p=0.017). The proportion of our surveyed patients who were willing to omit breast surgery was low. Patients who said they preferred to omit breast surgery overestimated the 5-year IBTR risk.

Increased Risk for Ipsilateral Breast Tumor Recurrence in Invasive Lobular Carcinoma after Accelerated Partial Breast Irradiation Brachytherapy.

The suitability criteria for accelerated partial breast irradiation (APBI) from the American Brachytherapy Society (ABS), American Society for Radiation Oncology (ASTRO), and The Groupe Européende Curiethérapie European SocieTy for Radiotherapy & Oncology (GEC-ESTRO) have significant differences. This is a single institution retrospective review of 946 consecutive patients with invasive breast cancer who underwent lumpectomy and APBI intracavitary brachytherapy from 2003 to 2018. Overall survival (OS), breast cancer-specific survival (BCSS), relapse-free survival (RFS), and ipsilateral breast tumor recurrence (IBTR) were estimated with Kaplan-Meier method. Median follow-up time was 60.2 months. Median age was 68 years (46-94 years). The majority of patients had estrogen receptor (ER)-positive disease (94%). There were 821 (87%) cases of invasive ductal carcinoma and 68 cases (7%) of invasive lobular carcinoma (ILC). The 5-year OS, BCSS, RFS, and IBTR were 93%, 99%, 90%, and 1.5%, respectively. Upon univariate analysis, ILC (hazard ratio [HR], 4.6; p=.008) and lack of nodal evaluation (HR, 6.9; p=.01) were risk factors for IBTR. The 10-year IBTR was 2.5% for IDC and 14% for ILC. While the ABS and ASTRO criteria could not predict IBTR, the GEC-ESTRO intermediate risk group was associated with inferior IBTR (p=.04) when compared to both low risk and high risk groups. None of the suitability criteria was able to predict RFS. These results show that APBI is an effective treatment for patients with invasive breast cancer. Expansion of the current eligibility criteria should be considered, although prospective validation is needed. Caution is required when considering APBI for patients with ILC. In a large retrospective review of 946 patients with early breast cancer treated with partial mastectomy and accelerated partial breast irradiation (APBI) intracavitary brachytherapy, this study demonstrates durable local control. Patients deemed unsuitable or high risk by the American Brachytherapy Society, American Society for Radiation Oncology, and European Society for Radiotherapy and Oncology guidelines were not at increased risk for ipsilateral breast tumor recurrence (IBTR), suggesting that expansion of the current criteria should be considered. Importantly, however, these results demonstrate that caution should be taken when considering APBI for patients with invasive lobular carcinoma, as these patients had relatively high risk for IBTR (10-year IBTR, 14%).

Interstitial multicatheter HDR-brachytherapy as accelerated partial breast irradiation after second breast-conserving surgery for locally recurrent breast cancer.

ABSTRACTOur aim was to evaluate the efficacy and toxicity of interstitial multicatheter high dose rate brachytherapy (imHDR-BRT) as accelerated partial breast irradiation (APBI) after second breast-conserving surgery (BCS) in patients with ipsilateral breast tumor recurrence (IBTR). Between January 2010 and December 2019, 20 patients with IBTR who refused salvage mastectomy (sMT) were treated with second BCS and post-operative imHDR-BRT as APBI. All patients had undergone primary BCS followed by adjuvant external beam radiotherapy. Median imHDR-BRT dose was 32 Gy delivered in twice-daily fractions of 4 Gy. Five-year IBTR-free survival, distant metastasis-free survival (DMFS), overall survival (OS) as well as toxicity and cosmesis were evaluated in the present retrospective analysis. Median age at recurrence and median time from the first diagnosis to IBTR was 65.1 years and 12.2 years, respectively. After a median follow-up of 69.9 months, two patients developed a second local recurrence resulting in 5-year IBTR free-survival of 86.8%. Five-year DMFS and 5-year OS were 84.6% and 92.3%, respectively. Grade 1–2 fibrosis was noted in 60% of the patients with no grade 3 or higher toxicity. Two (10%) cases of asymptomatic fat necrosis were documented. Cosmetic outcome was classified as excellent in 6 (37.5%), good in 6 (37.5%), fair in 3 (18.75%) and poor in 1 (6.25%) patient, respectively. We conclude that imHDR-BRT as APBI re-irradiation is effective and safe for IBTR and should be considered in appropriately selected patients.

Abstract PS1-01: Combined analysis of the WORTH 1 and WORTH 2 studies of ipsilateral breast tumor recurrence after breast conservative surgery without radiotherapyusing the “5-mm thick slice and 5-mm free margin method”

Abstract Background: Breast conserving surgery with radiotherapy is one of the standard treatment methods for early breast cancer. However, it is regarded as an option to treat elderly patients with small hormone receptor positive breast cancer with breast conserving surgery and hormone therapy without radiotherapy. Two sequential prospective studies were conducted to examine the efficacy of breast conserving surgery without radiotherapy from 2002. Patients and Methods: Primary breast cancer patients were divided into the WORTH 1 (n=123) group (Oct. 2002 and Mar. 2005) and the WORTH 2 (n=198) group (Dec. 2006 and Nov. 2011) and the data was retrospectively combined and analyzed. The eligibility criteria of the two sequential studies were a tumor ≥3cm determined by palpation, pathologically node negative by axillary dissection or sentinel node biopsy and M0, no preoperative treatment, postmenopausal patients ≥50 years of age at surgery, no tumor cells within 5 mm from the margins, no lymphatic invasion around the primary tumor, and estrogen receptor positive. The surgical specimens were sliced at 5 mm intervals and all the slices were examined microscopically. Postoperative radiotherapy was not conducted and adjuvant chemotherapy was optional. The patients were treated with tamoxifen or anastrozole in WORTH 1 and anastrozole in WORTH 2 for 5 years. Ipsilateral breast tumor recurrence (IBTR)-free survival and distant relapse-free survival (DRFS) were recorded as the interval from initial surgery until IRTR or distant relapse. The factors related to IBTR were evaluated using the proportional hazard model. Patients who did not develop IBTR or distant relapse were statistically censored at the time of the last follow-up or death. Survival rates were calculated using the Kaplan-Mayer method. Statistical analyses were conducted using the log rank test. Values < 0.05 were considered statistically significant. Results: The median age at surgery was 65 (range 50-84). The median tumor size was 1.5 cm (range 0-4.0 cm). The median follow-up period for IBTR was 95 months (range 4-192 months). Only 3 patients were treated with adjuvant chemotherapy. The 5- and 10-year overall survival rates were 98.7% and 95.1%, respectively and the 5- and 10-year distant DRFS rates were 99.3% and 96.3%, respectively. The 5- and 10-year IBTR free rates were 97.0% and 89.7%, respectively. Older patients had significantly less IBTR rates (5-year IBTR free rates: 95.8% for ≤64 vs. 98.1% for ≥65, p=0.019). There was no difference in IBTR rates between the large and small tumors (5-year IBTR free rates: 96.9% ≤1.4 cm vs. 96.8% for ≥1.5 cm, p=0.094). PR positivity had a significantly lower IBTR free rates (5-year IBTR free rates: 98.3% for PR positive vs. 91.5% for PR negative, p=0.009). The age at surgery (≤64, p=0.017, Hazard ratio 3.07, 95% CI 1.22-7.70) and the PR status (PR negative, p=0.024, Hazard ratio 2.54, 95% Cl 1.13-5.69) independently affected the IBTR rates. Both the 5- and 10-year IBTR free rates of the patients who were ≥65 at surgery and had PR positive tumors (n=136) were 98.4%. Conclusions: The findings suggest that the “5-mm thick slice and 5-mm free margin” method may be effective in selecting patients who can be treated with breast conserving surgery and hormone therapy without radiotherapy. Citation Format: Norikazu Masuda, Shozo Ohsumi, Reiki Nishimura, Sadako Akashi-Tanaka, Kimito Suemasu, Hideko Yamauchi, Eriko Tokunaga, Tadashi Ikeda, Tsunehiro Nishi, Hiroto Hayashi, Yuichi Iino, Yuichi Takatsuka, Hideo Inaji. Combined analysis of the WORTH 1 and WORTH 2 studies of ipsilateral breast tumor recurrence after breast conservative surgery without radiotherapyusing the “5-mm thick slice and 5-mm free margin method” [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 PS1-01.

TARGIT-R (Retrospective): 5-Year Follow-Up Evaluation of Intraoperative Radiation Therapy (IORT) for Breast Cancer Performed in North America.

Intraoperative radiation therapy (IORT) has been investigated for patients with low-risk, early-stage breast cancer. The The North American experience was evaluated by TARGIT-R (retrospective) to provide outcomes for patients treated in "real-world" clinical practice with breast IORT. This analysis presents a 5-year follow-up assessment. TARGIT-R is a multi-institutional retrospective registry of patients who underwent lumpectomy and IORT between the years 2007 and 2013. The primary outcome of the evaluation was ipsilateral breast tumor recurrence (IBTR). The evaluation included 667 patients with a median follow-up period of 5.1 years. Primary IORT (IORT at the time of lumpectomy) was performed for 72%, delayed IORT (after lumpectomy) for 3%, intended boost for 8%, and unintended boost (primary IORT followed by whole-breast radiation) for 17% of the patients. At 5years, IBTR was 6.6% for all the patients, with 8% for the primary IORT cohort and 1.7% for the unintended-boost cohort. No recurrences were identified in the delayed IORT or intended-boost cohorts. Noncompliance with endocrine therapy (ET) was associated with higher IBTR risk (hazard ratio [HR], 3.67). Patients treated with primary IORT who were complaint with ET had a 5-year IBTR rate of 3.9%. The local recurrence rates in this series differ slightly from recent results of randomized IORT trials and arenotably higher than in previous published studies using whole-breast radiotherapy for similar patients with early-stage breast cancer. Understanding differences in this retrospective series and the prospective trials will be critical to optimizing patient selection and outcomes going forward.

Abstract P2-16-27: Risk factors of ipsilateral breast tumor recurrence in primary breast cancer patients who achieved pathological complete response after neoadjuvant chemotherapy

Abstract Background: Pathologic complete response (pCR) is an early surrogate marker of long-term survival in human epidermal growth factor receptor 2-positive (HER2+) and triple negative breast cancer (TNBC). However, it is difficult to predict patients who should avoid breast-conserving therapy (BCT) even after achieving pCR by neoadjuvant chemotherapy (NAC) with respect to ipsilateral breast tumor recurrence (IBTR). We aimed to assess the risk of IBTR in pCR patients who underwent BCT after NAC. Patients and methods: We retrospectively reviewed clinicopathological characteristics of 178 TNBC or HER2+ primary breast cancer patients with pCR who underwent BCT after NAC in 2 institutes between 2002 and 2017. Histological type and grade were defined according to the World Health Organization classification system. Estrogen receptor (ER), progesterone receptor (PR), and HER2 status were determined from the surgical specimens. ER and PR were assessed by immunohistochemical staining. HER2 was considered positive if reported as 3+ on immunohistochemical staining or if those tumors reported as 2+ were amplified on fluorescence in situ hybridization (FISH). pCR was defined as no involvement of invasive ductal carcinoma in breast and lymph nodes. All patients who had node-positive before NAC had axillary lymph node dissection even if assessed as clinically node-negative after NAC (ycN0). The 5-year IBTR-free survival was estimated in each subtype. The risk factors of IBTR, including the age at diagnosis, clinical T-stage, clinical N-stage, histological grade, neoadjuvant regimen, pathological N-status, and postoperative chemotherapy, were estimated using the log-rank test for univariate analysis. P-values < 0.05 were considered statistically significant. Results: A median age of the 178 patients at diagnosis was 52 years (range, 30-72 years). At a median follow-up period of 5.4 years (range, 0.2-15.4 years), 5 patients (3%) had developed IBTR. Among the 178 patients, 82 patients had TNBC and 96 patients had HER2+ breast cancer. NAC with a combination of anthracycline and taxane regimens was sequentially delivered to 163 of the 178 patients (92%). In 96 HER2+ patients, trastuzumab containing regimen were done in 69 (72%) in NAC setting and 79 (82%) in adjuvant setting. Sentinel lymph node biopsy without axillary lymph node dissection was performed 98 (55%) of the patients. Seventy-nine (44%) had received axillary lymph node dissection. Subtype (ER+/HER2+, ER-/HER2+, or TNBC) after achieving pCR was not associated with 5-year IBTR (P= 0.6). In multivariate analysis, Clinical N-stage (N1 or more) was the only independent clinicopathological factor of associated 5-year IBTR in TNBC (P = 0.04). In HER2+ breast cancer, postoperative trastuzumab has a similar trend for 5-year IBTR (P = 0.07). Conclusions: We showed that clinical node-positive before NAC in TNBC and no receiving trastuzumab in HER2+ breast cancer were prognostic factor of 5-year IBTReven after achieving pCR. Citation Format: Naoko Matsuda, Naoki Hayashi, Ryu Tokui, Takahiro Nakayama, Hideko Yamauchi, Makoto Ishitobi. Risk factors of ipsilateral breast tumor recurrence in primary breast cancer patients who achieved pathological complete response after neoadjuvant chemotherapy [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 P2-16-27.

Minimally invasive tumor bed implant (MITBI) and peri-operative high-dose-rate brachytherapy (PHDRBT) for accelerated minimal breast irradiation (AMBI) or anticipated boost (A-PHDRBT-boost) in breast-conserving surgery for ductal carcinoma in situ.

PurposeTo evaluate our institutional experience of minimally invasive tumor bed implantation (MITBI) during breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) to deliver peri-operative high-dose-rate brachytherapy (PHDRBT) as accelerated minimal breast irradiation (AMBI) or anticipated boost (A-PHDRBT-boost).Material and methodsPatients older than 40, with clinical and radiological unifocal DCIS < 3 cm were considered potential candidates for accelerated partial breast irradiation (APBI) and were implanted during BCS using MITBI-technique. Patients who in final pathology reports showed free margins and no other microscopic tumor foci, received AMBI with PHDRBT (3.4 Gy BID in 5 days). Patients with adverse features received A-PHDRBT-boost with post-operative external beam radiotherapy (EBRT).ResultsForty-one patients were implanted, and 36 were treated and analyzed. According to final pathology, 24 (67%) patients were suitable for AMBI and 12 (33%) were qualified for A-PHDRBT-boost. Reoperation rate for those with clear margins was 16.6% (6/36); this rate increased to 33% (4/12) for G3 histology, and 66% (4/6) were rescued using AMBI. Early complications were documented in 5 patients (14%). With a median follow-up of 97 (range, 42-138) months, 5-year rates of local, elsewhere, locoregional, and distant control were all 97.2%. 5-year ipsilateral breast tumor recurrence rates (IBTR) were 5.6% (2/36), 8.3% (2/24) for AMBI, and 0% (0/12) for A-PHDRBT-boost patients. Both instances of IBTR were confirmed G3 tumors in pre-operative biopsies; no IBTR was documented in G1-2 tumors. Cosmetic outcomes were excellent/good in 96% of AMBI vs. 67% in A-PHDRBT-boost (p = 0.034).ConclusionsThe MITBI-PHDRBT program allows selection of patients with excellent prognoses (G1-2 DCIS with negative margins and no multifocality), for whom AMBI could be a good alternative with low recurrence rate, decrease of unnecessary radiation, treatment logistics improvement, and over-treatment reduction. Patients whose pre-operative biopsy showed G3 tumor, presents with inferior local control and more risk of reoperation due to positive margins.

Breast-conserving surgery without radiation in elderly women with early breast cancer

Background and objectivesIrradiation after breast-conserving surgery (BCS) decreases the incidence of ipsilateral breast tumor recurrence (IBTR) and breast cancer-related death. However, daily radiation treatments are burdensome to elderly patients, whose risk of IBTR is relatively low. Since 2001, we have offered BCS without radiation to patients meeting our selection criteria. This study assessed the prognosis of the patients who chose this option. MethodsBetween 2001 and 2014, 203 patients met the selection criteria: aged ≥60 years; pathologically node-negative, hormone-positive breast cancer; a negative surgical margin; and no lymphovascular invasion. Among these patients, 84 and 119 underwent BCS with or without radiation, respectively. IBTR, overall survival (OS), and breast cancer-specific survival (BCSS) were evaluated. ResultsThe median follow-up duration was 6.2 years. There were no significant differences in tumor size or the number of patients with adjuvant therapy between the groups. The 5-year IBTR rates were 0.9% and 1.6% in the non-irradiated and irradiated groups, respectively (p = 0.308). The 5-year OS rates were 94.1% and 98.7% (p = 0.391). Similarly, the 5-year BCSS rates were 97.2% and 98.7% (p = 0.812). ConclusionIt is suggested that the omission of irradiation could be an option for elderly breast cancer patients who satisfy our criteria.

Abstract OT2-03-01: Multicenter study to standardize and evaluate the efficacy of radiofrequency ablation therapy for early breast cancer (RAFAELO study)

Abstract Background: Early-stage breast cancer is increasingly detected by screening mammography, and we aim to establish radiofrequency ablation therapy (RFA) as a minimally invasive, cost-efficient, and cosmetically acceptable local treatment. In our Phase I study, localized tumors with a maximum diameter of 2 cm, preoperatively diagnosed by imaging and histopathology, were treated with RFA. A 90% complete ablation rate was confirmed histopathologically. Our phase II multicenter study of RFA without resection for early breast cancer will evaluate the long-term safety and efficacy of RFA as well as its cosmetic results, which are a perceived advantage of this technique. Trial design: This study is a Phase III, single-arm, multicenter study being conducted with the participation of 11 hospitals. In our experimental therapy, a radiofrequency electrode needle is inserted through the skin into the breast lesion under imaging guidance, followed by thermal ablation with radiofrequency waves. RFA will be conducted under general anesthesia. The Cool-tip™ RF Ablation Single Electrode Kit (Medtronic, CO, USA) will be used to standardize the evaluation of the ablation effect. After RFA, all patients will receive radiotherapy and systemic therapy according to the ER, HER2, tumor grade, and lymph node status of the primary tumor. Residual lesions after RFA will be assessed approximately 3 months after radiotherapy using imaging and pathological studies. All patients will undergo vacuum-assisted biopsy regardless of imaging results. If specimens show viable tumor tissue, additional excision will be performed. Follow-up evaluation for residual tumor, including clinical breast examination and diagnostic imaging (ultrasound, MRI, and mammography), will be performed yearly after RFA. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000012429. Eligibility criteria: Early breast cancer patients, who are lack of prior treatment for breast cancer and histologically confirmed ductal carcinoma with a single localized tumor of 1.5 cm or less in the greatest dimension and clinically node negative on preoperative imaging. Specific Aims: The primary endpoint is 5-year ipsilateral breast tumor recurrence(IBTR) rate, and the secondary endpoints are residual lesion rate, overall survival, DFS, and adverse events of RFA. Statistical methods: The IBTR rate should be similar to that with standard treatment (BCS). However, the IBTR after RFA alone may be higher by up to 10% than in the NSABP-B06 study; therefore the 5-year IBTR rate is estimated to be 6.3%. We calculated the required sample size based on the following assumptions: a clinically acceptable 5-year local recurrence-free survival rate of 90%, a one-sided significance level of 5% (alpha = 0.1, 2-sided), and power of 80% (beta = 0.2). Taking into account a drop-out rate of 10%, approximately 372 patients will be enrolled in the study. Present accrual and target accrual: The trial was activated in August 2013, with a total of 372 patients enrolled by the end of June 2018. Citation Format: Kinosita T, Takahashi M, Fujisawa T, Yamamoto N, Doihara H, Ohtani S, Futamura M, Takahashi M, Aogi K, Hojo T, Yoshida M, Shiino S, Tsuda H. Multicenter study to standardize and evaluate the efficacy of radiofrequency ablation therapy for early breast cancer (RAFAELO study) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-03-01.

Abstract GS4-03: RAPID: A randomized trial of accelerated partial breast irradiation using 3-dimensional conformal radiotherapy (3D-CRT)

Abstract Background Whole breast irradiation (WBI) after lumpectomy reduces the risk of local recurrence, thereby avoiding subsequent mastectomy. It is a key component of breast conserving therapy. WBI is usually given in daily fractions over 3-6 weeks. With accelerated partial breast irradiation (APBI), radiation is delivered over a week or less to the surgical cavity with a margin of normal tissue. It was introduced to provide treatment in a shorter more convenient form. 3D-CRT is an attractive approach as it is non-invasive and uses standard techniques for external beam RT that are widely available. The objective of the RAPID trial was to determine if APBI using 3D-CRT was not inferior to WBI following breast conserving surgery (BCS). Methods Women ≥40 years of age with axillary node-negative invasive ductal carcinoma, or ductal carcinoma in situ (DCIS) ≤3cm treated by BCS with clear margins of excision were eligible. Randomization was stratified for age (&amp;lt; or ≥50y), histology (DCIS alone or invasive breast cancer), tumor size (&amp;lt; or ≥1.5cm), ER status (+/-) if invasive disease, and treatment center. Patients were allocated to APBI using 3D-CRT (38.5Gy in 10 fractions delivered twice daily) or WBI (42.5Gy in 16 daily fractions or 50Gy in 25 daily fractions; boost radiation was permitted). The primary outcome was ipsilateral breast tumor recurrence (IBTR). Important secondary outcomes included radiation toxicity and nurse assessed adverse cosmesis (fair or poor on global assessment). The trial was designed to show that the 5-year IBTR rate in the APBI arm was not inferior to the WBI arm by more than 1.5% (hazard ratio [HR] ≤ 2.02) with 85% power and a one-sided alpha of 5%. Results From February 2006 to July 2011, 2135 patients from sites in Canada, Australia, and New Zealand were randomly assigned: 1070 to APBI and 1065 to WBI. The median follow-up was 8.6 years. The mean age of the study population was 61 years; 82% of patients had invasive breast cancer and 18% had DCIS only. For invasive cancers: 60% were &amp;lt; 1.5cm and 90% were ER positive. For DCIS tumors: 68% were &amp;lt; 1.5cm. A total of 65 IBTRs were observed. For the APBI patients, the 5-year and 8-year cumulative rates of IBTR were 2.3% and 3.0%, respectively. The corresponding data for the WBI patients were 1.7% and 2.8%. The HR for APBI versus WBI was 1.27, 90% confidence interval, 0.84 to 1.91. Acute radiation toxicity (occurring within 3 months of treatment start) e.g. radiation dermatitis and breast swelling was less in patients treated with APBI compared with WBI (≥ Grade 2, 28% vs 45%, p&amp;lt;0.001). Late radiation toxicity (beyond 3 months) e.g. breast induration and telangiectasia was greater in patients treated with APBI (≥ Grade 2, 32% vs 13%, p&amp;lt;0.001 and Grade 3, 4.5% vs 1.0%, p&amp;lt;0.001). Adverse cosmesis was higher in patients treated with APBI compared with WBI at 3 years (29% vs 17%, p&amp;lt;0.001) and at 5 years (32% vs 16%, p&amp;lt;0.001). Conclusions The APBI regimen used in our trial was non-inferior to WBI in preventing local recurrence. Although it was associated with less acute toxicity, an increase in late normal tissue toxicity and adverse cosmesis was observed with APBI. Citation Format: Whelan T, Julian J, Levine M, Berrang T, Kim D-H, Gu CS, Germain I, Nichol A, Akra M, Lavertu S, Germain F, Fyles A, Trotter T, Perera F, Balkwill S, Chafe S, McGowan T, Muanza T, Beckham W, Chua B, Olivotto I. RAPID: A randomized trial of accelerated partial breast irradiation using 3-dimensional conformal radiotherapy (3D-CRT) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS4-03.

Abstract OT2-01-04: Freezing instead of resection of small breast tumors (FROST): A study of cryoablation in the management of early stage breast cancer

Abstract Background/Objective: ACOSOG Z1072 demonstrated complete target tumor ablation in 92% of stage I invasive breast cancers treated with cryoablation prior to resection. We hypothesize that cryoablation can achieve complete tumor ablation and adequate local control in a selected population of women with early stage invasive breast cancer managed with cryoablation alone, without planned surgical resection. Methods: The trial is a phase II, single-arm, multicenter study open to women age 50 and older with core needle biopsy-proven clinical stage I, T1, clinically node negative (N0), unifocal, hormone receptor positive, HER2/neu-negative invasive ductal carcinoma measuring ≤1.5 cm by mammography (MG), ultrasound (US), and MRI. Once registered, subjects will undergo US-guided cryoablation followed 6 months later by an US-guided core biopsy of the cryoablated lesion to confirm the absence of residual viable disease. Following cryoablation, subjects will also begin a minimum 5-year course of adjuvant endocrine therapy and serial MG, US, and MRI. Whole breast radiotherapy (WBRT) is optional for subjects age 70+ (stratum I) and mandatory for women age 50-69 (stratum 2). Sentinel node biopsy (SNBx) is optional in both cohorts. All subjects found to have residual or recurrent disease will undergo standard surgical resection. Study SchemaRegistrationCryoablation6 MonthsSemiannualAnnualResectionAge 50+, tumor size ≤ 1.5 cm, unifocal, N0, biopsy proven invasive breast cancerFollowed by endocrine therapy (all patients); WBRT (Stratum 2); SNBx (optional)MG, US, MRI, needle biopsy; resection of residual cancer or serial follow up if absentUnilateral US or MG X 3 yearsBilateral MG and MRIRecurrent/residual breast or axillary cancer The trial was activated in June 2016. The study is currently open at 6 sites with up to 30 sites planned. A total of 110 eligible subjects will be enrolled in each stratum for total accrual goal of 220. Enrollment is planned over 3 years followed by 5 years of follow-up. Results: The primary endpoint of the study will be to determine the rate of complete tumor ablation in patients treated with cryoablation, defined as absence of residual viable carcinoma detected by core needle biopsy of the ablation site performed 6-months post-cryoablation. The secondary endpoint will be to determine the 5-year ipsilateral breast tumor recurrence rate in patients treated with cryoablation without subsequent resection. Local recurrence will be defined as recurrence of cancer within the index quadrant confirmed histologically by needle biopsy. Breast cosmesis (assessed by BCCT.core) and adverse events will also be evaluated. Conclusions: If the FROST Trial is successful at achieving complete ablation in ≥ 80% of study subjects, the trial will provide an important foundation for establishing cryoablation as an alternative to conventional therapy in selected women with early stage invasive breast cancer. If interested, please contact Pam Ellis, clinical coordinator, at (925)460-6080 or pellis@sanarus.com. Citation Format: Coronado GM, Ho ET, Holmes DR. Freezing instead of resection of small breast tumors (FROST): A study of cryoablation in the management of early stage breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT2-01-04.

Clinical risk score to predict likelihood of recurrence after ductal carcinoma in situ treated with breast-conserving surgery

A majority of women with ductal carcinoma in situ (DCIS) receive breast-conserving surgery (BCS) but then face a risk of ipsilateral breast tumor recurrence (IBTR) which can be either recurrence of DCIS or invasive breast cancer. We developed a score to provide individualized information about IBTR risk to guide treatment decisions. Data from 2762 patients treated with BCS for DCIS at centers within the National Comprehensive Cancer Network (NCCN) were used to identify statistically significant non-treatment-related predictors for 5-year IBTR. Factors most associated with IBTR were estrogen-receptor status of the DCIS, presence of comedo necrosis, and patient age at diagnosis. These three parameters were used to create a point-based risk score. Discrimination of this score was assessed in a separate DCIS population of 301 women (100 with IBTR and 200 without) from Kaiser Permanente Northern California (KPNC). Using NCCN data, the 5-year likelihood of IBTR without adjuvant therapy was 9% (95% CI 5-12%), 23% (95% CI 13-32%), and 51% (95% CI 26-75%) in the low, intermediate, and high-risk groups, respectively. Addition of the risk score to a model including only treatment improved the C-statistic from 0.69 to 0.74 (improvement of 0.05). Cross-validation of the score resulted in a C-statistic of 0.76. The score had a c-statistic of 0.67 using the KPNC data, revealing that it discriminated well. This simple, no-cost risk score may be used by patients and physicians to facilitate preference-based decision-making about DCIS management informed by a more accurate understanding of risks.

Delay in radiotherapy is associated with an increased risk of disease recurrence in women with ductal carcinoma in situ.

The current study was conducted to examine the association between ipsilateral breast tumor recurrence (IBTR) and the timing of radiotherapy (RT) in women with ductal carcinoma in situ (DCIS) undergoing breast-conserving surgery (BCS). Women with DCIS who were treated with BCS and RT from 1980 through 2010 were identified from a prospectively maintained database. IBTR rates, measured from the time of RT completion, were compared between those who initiated RT ≤8 weeks, >8 to 12 weeks, and >12 weeks after the completion of surgery. The association between RT timing and IBTR was evaluated by Kaplan-Meier and log-rank analyses; Cox modeling was used for multivariable analysis. A total of 1323 women met the inclusion criteria. The median follow-up was 6.6 years, with 311 patients followed for ≥10 years. A total of 126 IBTR events occurred. Patients were categorized by RT timing: 806 patients (61%) with timing of ≤8 weeks, 386 patients (29%) with timing of >8 to 12 weeks, and 131 patients (10%) with timing >12 weeks. The 5-year and 10-year IBTR rates were 5.8% and 13.0%, respectively, for RT starting ≤8 weeks after surgery; 3.8% and 7.6%, respectively, for RT starting >8 to 12 weeks after surgery; and 8.8% and 23.0%, respectively, for an RT delay >12 weeks after surgery (P = .004). On multivariable analysis, menopause (hazard ratio [HR], 0.54; P = .0009) and endocrine therapy (HR, 0.45; P = .002) were found to be protective against IBTR, whereas a delay in RT >12 weeks compared with ≤8 weeks was associated with a higher risk of IBTR (HR, 1.92; P = .014). There was no difference in IBTR noted between RT initiation at ≤8 weeks and initiation at >8 to 12 weeks after BCS (P = .3). A delay in RT >12 weeks is associated with a significantly higher risk of IBTR in women undergoing BCS for DCIS. Efforts should be made to avoid delays in starting RT to minimize the risk of disease recurrence. Cancer 2018;124:46-54. © 2017 American Cancer Society.

Omitting re-excision for focally positive margins after breast-conserving surgery does not impair disease-free and overall survival

PurposeIn contrast to other countries, the Dutch breast cancer guideline does not recommend re-excision for focally positive margins after breast-conserving surgery (BCS) in invasive tumor and does recommend whole-breast irradiation including boost. We investigated whether omitting re-excision as compared to performing re-excision affects prognosis with a retrospective population-based cohort study.MethodsThe total cohort included 32,119 women with primary BCS for T1–T3 breast cancer diagnosed between 2003 and 2008 from the nationwide Netherlands cancer registry. The subcohort included 10,433 patients in whom the resection margins were registered. Outcome measures were 5-year ipsilateral breast tumor recurrence (IBTR) rate, 5-year disease-free survival (DFS) rate, and 10-year overall survival (OS) rate.ResultsIn the total cohort, 25,878 (80.6%) did not have re-excision, 2368 (7.4%) had re-excision by BCS, and 3873 (12.1%) had re-excision by mastectomy. Five-year IBTR rates were 2.1, 2.8, and 2.9%, respectively (p = 0.001). In the subcohort, 7820 (75.0%) had negative margins without re-excision, 492 (4.7%) had focally positive margins without re-excision, 586 (5.6%) had focally positive margins and underwent re-excision, and 1535 (14.7%) had extensively positive margins and underwent re-excision. Five-year IBTR rate was 2.3, 2.9, 1.1, and 2.9%, respectively (p = 0.099). Compared to omitting re-excision, performing re-excision for focally positive margins was associated with lower risk of IBTR (adjusted HR 0.30, 95% CI 0.11–0.82), but not with DFS (adjusted HR 0.83 95% CI 0.59–1.17) nor with OS (adjusted HR 1.17 95% CI 0.87–1.59).ConclusionOmitting re-excision in breast cancer patients for focally positive margins after BCS does not impair DFS and OS, provided that whole-breast irradiation including boost is given.

Abstract P3-13-13: Breast-conserving surgery plus hormone therapy without irradiation in elderly women with early breast cancer

Abstract Background The meta-analysis of the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) revealed that whole-breast irradiation after breast conserving surgery (BCS) decreased ipsilateral breast tumor recurrence (IBTR) and breast cancer-related death. However, elderly patients can find daily hospital attendance difficult, and their IBTR risk is low. A randomized control trial was performed in women aged ≥70 years with hormone-positive breast cancer to investigate the usefulness of breast-conserving therapy without irradiation (Hughes et al. N Engl J Med 2004). Since September 2001, we have offered BCS plus hormone therapy without irradiation in patients who satisfy the following criteria: age ≥60 years; pathologically node negative, hormone-positive breast cancer; a negative surgical margin; and no lymphovascular invasion. We assessed prognosis in patients who chose this option. Patients and methods Between September 2001 and December 2014, 219 patients met the inclusion criteria; 90 and 129 patients underwent BCS plus hormone therapy with or without irradiation, respectively. The cumulative IBTR incidence and overall survival (OS) for the groups was evaluated. A negative surgical margin was defined as a margin of ≥5 mm. Results The median ages at operation were 73 years (range, 60–88 years) and 65 years (range, 60–80 years) for the without and with irradiation groups, respectively (p &amp;lt;0.001). There were no significant differences in tumor size, lymph node metastasis, or adjuvant therapy between the groups. The median follow-up duration is presently 4.6 years. IBTR was observed in 5 (3.9%) and 1 (1.1%) patient(s) in the without and with irradiation groups, respectively (p = 0.192). The 5-year IBTR cumulative incidences were 0.9% and 2.2%, and the 10-year were 6.7% and 2.2%, for the without and with irradiation groups, respectively (p = 0.390). The 5-year OS rates were 93.8% and 98.5%, and the 10-year OS rates were 89.7% and 94.0 for the without and with irradiation groups, respectively (p = 0.205). Conclusion BCS plus hormone therapy without irradiation in elderly patients is an appropriate option. Citation Format: Inoue H, Hirano A, Ogura K, Hattori A, Yukawa H, Sakaguchi S, Matsuoka A, Tanaka N, Kodera A, Kamimura M, Fujibayashi M, Naritaka Y, Shimizu T. Breast-conserving surgery plus hormone therapy without irradiation in elderly women with early breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-13-13.

Safety of breast-conserving treatment for triple-negative breast cancer

To investigate the effect of risk factors on ipsilateral breast tumor recurrence (IBTR) and distant disease-free survival (DDFS) for patients with triple-negative breast cancer (TNBC) who underwent breast-conserving treatment (BCT). A series of 1 835 patients with primary breast cancer treated with BCT in a single institute between December 1999 and August 2010 were analyzed retrospectively. Totally 1 614 patients, whose characteristics were intact, were analyzed to compare their outcomes with respect to the incidence of IBTR, DDFS and disease-free survival (DFS). All of patients were female. Median age was 47 years (ranging 21 to 92 years, interquartile range 14 years). According to the immunohistochemical results of the patients, 1 614 cases were divided into TNBC group (n=308) and non-TNBC group (n=1 306). The risk factors of relapse after breast-conserving treatment (age at diagnosis, spread to axillary lymph nodes, hormone receptor status, neoadjuvant chemotherapy, and maximal tumor diameter, human epidermal growth factor receptor 2 (HER-2) status, preoperative MRI, the location and extent of the tumor bed defined by CT scans for electron boost planning as part of breast radiotherapy) were studied.χ(2) test was used to compare the distribution of baseline characteristics among subtypes. The probability of survival (or relapse occurrence), and DDFS were calculated using the Kaplan-Meier method. Cumulative incidence functions were used to describe the cumulative hazard from LR, IBTR and DDFS in the presence of competing risks. A total of 1 614 women with primary breast cancer underwent a breast-conserving surgery followed by radiotherapy. The median follow-up period was 77 months (interquartile range 36 months). One hundred and forty patients (8.6%) were lost to follow-up. Overall 5-year IBTR rate was 3.1% (95% CI: 2.2% to 4.0%), 5-year DDFS rate was 95.8% (95% CI: 94.9% to 96.7%) and 5-year DFS rate was 93.8% (95% CI: 92.7% to 94.9%). Lymph nodal involvement (HR=3.03, 95% CI: 1.66 to 5.51, P=0.000) and use of CT information in boost field planning (HR=0.40, 95% CI: 0.20 to 0.80, P=0.010) were associated significantly with IBTR in Cox multivariable analysis. Multivariable analysis showed that TNBC doesn't have a significantly increased risk of IBTR compared with the non-TNBC subtype (HR=0.90, 95% CI: 0.50 to 1.76, P=0.78). TNBC was not an independent risk factor for DDFS or DFS. The multivariable model showed significant effect of nodal status and age at diagnosis on 5-year DDFS rate and 5-year DFS rate. Breast-conserving treatment for TNBC is not associated with increased IBTR compared with non-TNBC subtype. Use of CT information in boost field planning can reduce the risk of ipsilateral breast tumor recurrence for patients undergoing BCT.

Final results from a multicenter prospective study ( JROSG 05-5) on postoperative radiotherapy for patients with ductal carcinoma in situ with an involved surgical margin or close margin widths of 1 mm or less.

This multicenter prospective study ( Japanese Radiation Oncology Study Group: JROSG 05-5) aimed to evaluate the effectiveness of postoperative radiotherapy (PORT) in patients with ductal carcinoma in situ (DCIS) with an involved surgical margin or close margin widths of ≤1 mm or less. PORT consisted of whole-breast irradiation (50 Gy in 25 fractions) followed by boost irradiation (10 Gy in 5 fractions). Eligibility criteria were as follows: (i) DCIS without an invasive carcinoma component, (ii) age between 20 and 80 years old, (iii) involved margin or close margin widths of ≤1 mm, (iv) refusal of re-resection, (v) performance status of 0–2, and (vi) written informed consent. The primary endpoint was ipsilateral breast tumor recurrence (IBTR), and secondary endpoints were overall survival (OS), relapse-free survival (RFS), recurrence patterns, and adverse events. A total of 37 patients from 12 institutions were enrolled from January 2007 to May 2009. The median follow-up time was 62 months (range, 28–85 months). The median pathological tumor size was 2.5 cm (range, 0.3–8.5 cm). Of the 37 patients, 21 had involved margins, and 16 had close margins. The 5-year IBTR, OS and RFS rates were 6% (95% confidence interval [CI]: 2–21), 97% (95% CI: 83–99) and 91% (95% CI: 77–97), respectively. Two patients developed local recurrence at the original site after 39 and 58 months. No severe adverse events were found. Our study suggests that this PORT regimen could be a treatment option for patients with DCIS with involved margin or close margin who don't desire re-resection.

The Value of Ipsilateral Breast Tumor Recurrence as a Quality Indicator: Hospital Variation in the Netherlands.

All Dutch hospitals are obliged to report their 5-year ipsilateral breast tumor recurrence (IBTR) rate after breast cancer surgery. Experts decided that these rates should not exceed 5 %. This study determined the value of IBTR as an indicator to compare quality of care between hospitals. All patients with breast cancer (pT1-3, any N, M0) who underwent surgery in 1 of 92 Dutch hospitals from 2003 to 2006 were identified in the Netherlands Cancer Registry. Data of recurrence was retrieved from hospital records. Five-year IBTR rates for breast-conserving surgery (BCS) and mastectomy were calculated by using the Kaplan-Meier method. Hospital variation was presented in funnel plots. Multivariate analysis was used to assess hospital characteristics associated with IBTR rates. A total of 40,892 breast cancer patients were included. The overall 5-year IBTR rate was 2.85 % (95 % confidence interval 2.68-3.03) and was significantly lower for BCS than for mastectomy (2.38 vs. 3.45 %, p < 0.001). IBTR rates decreased over time in both groups. Rates varied between 0.77 and 5.70 % between hospitals. When random variation is taken into account, only extremely high IBTR rates can be detected as deviant from the target value of 5 %. Adjusting for tumor and patient characteristics, analyses showed that a higher volume of mastectomies is associated with lower IBTR rates. Our population-based findings show that IBTR rates in the Netherlands are low and have improved over time. The 5-year IBTR rate as an indicator for quality of care of individual hospitals is of limited value.

Retrospective Analysis of Risk Factors for Regional Recurrence for pN1 Patients After Breast Conserving Surgery

Retrospective Analysis of Risk Factors for Regional Recurrence for pN1 Patients After Breast Conserving Surgery