Extensive Intraductal Component Research Articles

Abstract GS02-08: Five-year outcomes of the IDEA trial of endocrine therapy without radiotherapy after breast-conserving surgery for postmenopausal patients age 50-69 with genomically-selected favorable Stage I breast cancer

Abstract Background: Multiple studies have shown a low risk of ipsilateral breast events (IBE) or other recurrences for selected patients age 65-70 or older with Stage I breast cancers treated with breast conserving surgery (BCS) and endocrine therapy (ET) without adjuvant radiotherapy (RT). We designed a prospective single-arm trial, IDEA (Individualized Decisions for Endocrine therapy Alone), to see if younger postmenopausal patients could also be successfully treated without RT, adding a genomic assay to classic selection factors. Methods: Postmenopausal patients aged 50-69 with pT1N0 unifocal invasive breast cancer with margins 2 mm or wider after BCS whose tumors were ER+, PR+, and Her2- with Oncotype DX 21-gene recurrence score (RS) 18 or lower were eligible to avoid RT if they consented to take at least 5 years of ET and surveillance on study. The primary endpoint was the rate of breast cancer recurrence at 5 years of follow-up after BCS. A valid 5–year assessment was defined as a clinical assessment within 4 months prior to the 5-year anniversary or later. Follow-up time was calculated from the date of BCS until first recurrence [ipsilateral breast events (IBE) or regional or distant failures] or to last clinical follow-up. The time-to-event endpoint was calculated using the product-limit method of Kaplan and Meier measured from the date of BCS. Results: 200 eligible patients were enrolled from 13 US institutions between June 2015 and October 2018. Median age was 63 years (IQR 58-66); mean RS was 11.2 (SD 4.8). Tumors were grade 1 in 85 patients, grade 2 in 109, and grade 3 in 6. Mean tumor size was 10 mm (SD 4.6). Lymphovascular invasion was present in 16 tumors and an extensive intraductal component in 11. Median follow-up time was 5.21 years (IQR 5.01-5.97); 8 of 14 patients with less than 56 months of follow-up were lost to follow-up. Overall and breast cancer-specific survival rates at 5 years were both 100%; 2 deaths occurred later than 5 years. The 5-year freedom from recurrence was 99% (95% CI, 96%-100%). One of the two events occurring by 5 years was an isolated axillary recurrence at 21 months treated with axillary dissection and breast and regional nodal irradiation. The other was an IBE at 49 months, treated with repeat BCS. Both these patients had been compliant with ET. Six additional patients recurred later than 5 years after BCS (5 IBEs, 1 IBE plus regional recurrence). Crude rates of IBE for the entire follow-up period for patients aged 50-59 and 60-69 were 3.3% (2/60) and 3.6% (5/140), respectively; crude rates of overall relapse were 5.0% (3/60) and 3.6% (5/140). Conclusions: This multicenter trial of ET without RT following BCS achieved a very low risk of relapse for postmenopausal patients with Stage I cancers using a genomic assay in combination with classic clinical and biologic features for treatment selection, including for patients younger than age 60. IDEA demonstrates a 5-year probability of recurrence consistent with or lower than the 4% risk estimated a priori, and the patients accrued were younger when compared to prior prospective trials (e.g., PRIME II, minimum age 65; CALGB 9343, minimum age 70; LUMINA, median age 67). The results of ongoing NRG BR007 trial, which randomly allocates women meeting these eligibility criteria to receive RT or not, and similar randomized and single-arm studies will help determine whether the option of avoiding initial RT can be offered to a broader group of women than current guidelines recommend. Long-term follow-up beyond the 5-year required period of ET will be important to determine if the risk of recurrence increases, particularly after discontinuation of ET. Citation Format: Reshma Jagsi, Kent Griffith, Eleanor Harris, Jean Wright, Abram Recht, Alphonse Taghian, Lucille Lee, Meena Moran, William Small, Candice Johnstone, Asal Rahimi, Gary Freedman, Mahvish Muzaffar, Bruce Haffty, Kathleen Horst, Simon Powell, Jody Sharp, Michael Sabel, Anne Schott, Mahmoud El-Tamer. Five-year outcomes of the IDEA trial of endocrine therapy without radiotherapy after breast-conserving surgery for postmenopausal patients age 50-69 with genomically-selected favorable Stage I breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS02-08.

Abstract PO2-01-12: Preoperative cryoablation in 52 Her2- Luminal invasive ductal carcinomas ≤ 2cm. Analysis of the tumor specimen

Abstract Objective: 1st: Assess the presence of residual infiltrating component in the surgical specimen of patients with Luminal Her2- tumors ≤ 2cm and ultrasound-negative axilla, following ultrasound-guided cryoablation. 2nd: Demonstrate that preoperative seed placement prior to cryoablation does not interfere with tumor cell elimination by freezing. Methods: Between April 2021 and April 2023, we performed preoperative cryoablation on 52 patients aged 53 to 79 years (mean 64) with 52 unifocal invasive ductal carcinomas (IDC) measuring 4 to 20 mm (mean 10), low grade (24 G1, 28 G2), 31 Luminal A and 21 B, Ki67 between 3 and 30% (mean 13). On ultrasound, all IDCs were visible and axilla-negative. 26 of them (50%) were referred from the screening program of the Community of Madrid. The tumor-to-skin surface distance ranged from 2 to 18 mm (mean 9 mm). All patients underwent mammography-tomosynthesis, staging, and biopsy under ultrasound guidance. The minimum time elapsed until surgery was 6 days, and the maximum was 78 days (mean 22). All patients underwent mammography-tomosynthesis, staging, and biopsy under ultrasound guidance. MRI was performed to rule out extensive intraductal component in 17 out of 20 patients with associated intraductal carcinoma (IDC) in the diagnostic biopsy. Preoperative marking with ferromagnetic seed placement was performed in all cases prior to cryoablation, using a single dose of anesthesia and through the same skin access. We used the ICEfx Galil Boston Scientific cryoablation system with 17G or 14G needles, applying the standard triple-phase protocol: freezing-passive thawing-freezing for approximately 40 minutes. The correct placement of the seed was subsequently confirmed by mammography. Results: There were no significant complications in any case. Out of 52 low-risk unifocal IDCs: -32 were pure IDCs (without associated intraductal component in diagnostic biopsy): no residual IDC was identified in the tumor specimen. -20 were mixed IDCs (with associated IDC in the diagnostic biopsy): *In 4 cases, residual IDC was found in the surgical specimen, with some foci of IDC remaining at the periphery of the post-cryoablation necrosis. *In 8 patients, foci of IDC were detected distant from the cryoablation zone. The pathologist determined that all samples had tumor-free margins. Conclusions: Cryoablation is effective in 100% of cases for pure infiltrating tumors ≤ 2cm. The presence of scattered IDC nests away from the cryoablation zone or at the margin of fat necrosis does not indicate technique failure, as all surgical specimens were determined to have tumor-free margins by the pathologist. For mixed infiltrating tumors, the ice ball should broadly cover the tumor size estimated by ultrasound and MRI. Standard adjuvant treatment will equalize the risk of recurrence with conventional lumpectomy. Table 1: 52 cases IDC unifocal ≤2cm Table 2: IDC Pure ≤2cm. Table 3: IDC mixed: IDC+DCIs ≤2cm Analysis of surgical specimen Citation Format: Maria José Roca Navarro, Pilar Zamora, Ylenia Navarro Monforte, Diego Garrido Alonso, Vicenta Córdoba Chicote, Teresa Diaz de Bustamante Durban, José María Oliver Goldaracena, Laura Yebenes Gregorio, Covadonga Marti, Jose Ignacio Sanchez-Mendez, Elisa Moreno, Laura Frías Aldeguer, Adolfo Loayza Galindo, Alberto Berjón García, Marcos Melendez Gisper, Carmen Martín Hervás, Lara Miralles, Cristina Escabias del Pozo, Younes Abadi, Elisa York Pineda, Gonzalo Garzón Moll, David Hardisson Hernáez, Alicia Hernández Gutiérrez, César Casado Sánchez, Virginia Martínez Marín, Shirin Zarbakhsh, Joaquin Gomez Ramirez. Preoperative cryoablation in 52 Her2- Luminal invasive ductal carcinomas ≤ 2cm. Analysis of the tumor specimen [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-01-12.

Exploration of tumor size measurement methods in preoperative breast cancer assessment using whole-body silicon photomultiplier PET: feasibility and first results.

Whole-body silicon photomultiplier positron emission tomography (WB SiPM PET) could be used to diagnose breast cancer spread before lumpectomy. We aimed to investigate the method of measuring the tumor size by WB SiPM PET as a basis for diagnosing breast cancer spread in the breast. We retrospectively reviewed 35 breast cancer lesions in 32 patients who underwent WB SiPM PET/CT in the prone position as preoperative breast cancer examinations from September 2020 to March 2022. In all cases, a 20-mm spherical VOI was placed in the normal mammary gland to measure the mean standardised uptake value (SUVmean) and the standard deviation (SD) of 18F-fluorodeoxyglucose (FDG) uptake. We prepared four types of candidates (SUVmean + 2 SD, SUVmean + 3 SD, 1.5 SUVmean + 2 SD, 1.5 SUVmean + 3 SD) for thresholds for delineating tumor contours on PET images. On the semiautomatic viewer soft, the maximum tumor sizes were measured at each of the four thresholds and compared with the pathological tumor sizes, including the extensive intraductal component (EIC). The lesion detection sensitivity was 97% for WB SiPM PET. PET detected 34 lesions, excluding 4-mm ductal carcinomas in situ (DCIS). PET measurements at the '1.5 SUVmean + 2 SD' threshold demonstrated values closest to the pathological tumor sizes, including EIC. Moreover, '1.5 SUVmean + 2 SD' had the highest concordance (63%). The study demonstrated that among various PET thresholds, the '1.5 SUVmean + 2 SD' threshold exhibited the best performance. However, even with this threshold, the concordance rate was limited to only 63%.

Do HER2-Low Tumors Have a Distinct Clinicopathologic Phenotype?

Breast cancer subtypes, distinguished by hormone receptor (HR) and HER2 status, have different clinicopathologic features. With recognition of the clinical relevance of HER2-low, there is debate as to whether this is a distinct subtype. Our study aimed to determine whether HER2-low breast cancers have specific clinicopathologic features that differ from those of HER2-negative and HER2-positive cancers. A total of 11,072 patients undergoing upfront surgery from 1998 to 2010 were identified from a single-institution prospectively maintained database. HER2 status was classified by immunohistochemistry (IHC)/fluorescence in situ hybridization (FISH) as HER2 negative (41.2%), HER2 low (45%; IHC 1+ or 2+ with negative FISH), and HER2 positive (13.7%), and stratified by HR status. Univariate (UVA) and multivariable multinomial logistic regression analysis (MVA) were performed to determine associations among variables and subtypes. Compared with HER2-negative tumors, HER2 low was associated with lymphovascular invasion [odds ratio (OR) 1.2, 95% confidence interval (CI) 1.06-1.36; p = 0.003], multifocality (OR 1.26, 95% CI 1.12-1.42; p < 0.001), nodal micrometastasis (OR 1.15, 95% CI 1.02-1.31; p = 0.024), and lower rates of ≥ 3 positive nodes (OR 0.77, 95% CI 0.66-0.90, p = 0.001). When stratified by HR expression, in both HR-positive and HR-negative tumors, age and multifocality were associated with HER2 low on UVA. On MVA, no variables were independently associated with both HR-negative and HR-positive/HER2-low tumors compared with HER2-negative tumors. In contrast, HER2-positive tumors, regardless of HR status, were associated with multifocality and an extensive intraductal component. Clinicopathologic features of HER2-low tumors appear to be primarily related to HR status. Our findings do not support the characterization of HER2 low as a separate subtype.

Multitask deep learning on mammography to predict extensive intraductal component in invasive breast cancer.

To develop a multitask deep learning (DL) algorithm to automatically classify mammography imaging findings and predict the existence of extensive intraductal component (EIC) in invasive breast cancer. Mammograms with invasive breast cancers from 2010 to 2019 were downloaded for two radiologists performing image segmentation and imaging findings annotation. Images were randomly split into training, validation, and test datasets. A multitask approach was performed on the EfficientNet-B0 neural network mainly to predict EIC and classify imaging findings. Three more models were trained for comparison, including a single-task model (predicting EIC), a two-task model (predicting EIC and cell receptor status), and a three-task model (combining the abovementioned tasks). Additionally, these models were trained in a subgroup of invasive ductal carcinoma. The DeLong test was used to examine the difference in model performance. This study enrolled 1459 breast cancers on 3076 images. The EIC-positive rate was 29.0%. The three-task model was the best DL model with an area under the curve (AUC) of EIC prediction of 0.758 and 0.775 at the image and breast (patient) levels, respectively. Mass was the most accurately classified imaging finding (AUC = 0.915), followed by calcifications and mass with calcifications (AUC = 0.878 and 0.824, respectively). Cell receptor status prediction was less accurate (AUC = 0.625-0.653). The multitask approach improves the model training compared to the single-task model, but without significant effects. A mammography-based multitask DL model can perform simultaneous imaging finding classification and EIC prediction. The study results demonstrated the potential of deep learning to extract more information from mammography for clinical decision-making. • Extensive intraductal component (EIC) is an independent risk factor of local tumor recurrence after breast-conserving surgery. • A mammography-based deep learning model was trained to predict extensive intraductal component close to radiologists' reading. • The developed multitask deep learning model could perform simultaneous imaging finding classification and extensive intraductal component prediction.

Extensive intraductal component as a factor determining local recurrence of breast cancer: a systematic review and meta-analysis.

Breast-conserving surgery and mastectomy are standard surgical options for breast cancer. However, some patients experience a local recurrence after the operation. Many factors have been identified as a risk of local recurrence. Extensive intraductal component (EIC) was found as one of the major risks of the recurrence. Nevertheless, there were neither any systematic reviews nor controlled trials focused on EIC. This study aims to identify the impact of EIC on the local recurrence of breast cancer. We searched all relevant studies published between the inception to December 2020. All electronic data from PubMed and Scopus databases were extracted for evaluation of EIC as a factor of the recurrence. Local recurrence was a primary outcome between EIC-positive group and EIC-negative group. Margin status and adjuvant radiation were focused as a subgroup analysis. The Newcastle Ottawa Scale was applied for quality assessment of included studies and RevMan 5.3 program was used to estimate the effect of the results. The odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. A total of 32 studies, comprising 4,290 and 15,143 patients in the EIC-positive and EIC-negative groups respectively, were retrieved and met selection criteria. All included studies were at low to intermediate risk of bias. There was a statistically significant difference in local recurrence between EIC-positive patients and EIC-negative patients (OR =2.73; 95% CI: 2.42-3.07; P<0.00001). However, there was not any significant difference in patients who had negative margin (OR =1.97; 95% CI: 0.92-4.19; P=0.36) or received any adjuvant irradiation (OR =1.58; 95% CI: 0.55-4.54; P=0.24). EIC increases the risk of local recurrence, especially in breast-conserving surgery patients. However, there are a limited number of populations to analyze in subgroup analysis, the rate of local recurrence between two groups is not different in patients who had negative margin or received postoperative irradiation.

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

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

Do HER2 low tumors have a distinct clinicopathologic phenotype?

570 Background: Clinicopathologic features of breast cancer subtypes defined by hormone receptor (HR) and HER2 status differ. These analyses classified HER2 IHC &lt;3+ with negative FISH as HER2-. With the recognition of the clinical relevance of HER2 low, there is debate as to whether this is a distinct subtype. We sought to determine if features of HER2 low tumors differ from HER2- and HER2+ after controlling for HR status. Methods: Patients undergoing upfront surgery from 1998 to 2010 were identified from a prospectively maintained institutional database. HER2 status was classified by IHC/FISH analysis as HER2-, HER2 low (IHC 1+ or 2+ with negative FISH), and HER2+ (IHC 3+ or FISH +) and stratified by HR status. Univariable (UVA) and multivariable multinomial logistic regression analysis (MVA) were performed to determine associations among variables and subtypes. Results: 11,323 tumors from 11,072 patients were included. 5,104 (45%) were HER2 low, 41.2% were HER2- and 13.6% were HER2+. On MVA stratified by HER2 status only, compared to HER2- tumors, HER2 low was associated with LVI (OR 1.2 [95% CI 1.06-1.36]; p=.003), multifocality (OR 1.26 [95% CI, 1.12-1.42]; p&lt;.001), nodal micrometastasis (OR 1.15 [95% CI, 1.02-1.31]; p=.024), and lower rates of &lt;3 positive nodes (OR 0.77 [95% CI, 0.66-0.90], p=.001). HER2+ was associated with younger age, high grade, multifocality, extensive intraductal component (EIC), and pN2/3 nodal stage. Clinicopathologic features stratified by HR and HER2 status are shown in the table. On UVA, in both HR+ and HR– tumors, age and multifocality were associated with HER2 low, and LVI, multifocality, and EIC with HER2+ compared to HER2- tumors. On MVA, no variables were independently associated with both HR+ and HR-/HER2 low tumors compared to HER2-. In contrast, HER2+ tumors regardless of HR status were significantly associated with multifocality and EIC. Conclusions: HER2 low breast cancer features seem to be driven by HR status and HER2 overexpression. We do not have enough evidence to support the interpretation of HER2 low as a distinct subtype. [Table: see text]

Risk Factors for Positive Margins in Breast-Conserving Surgery.

Introduction Breast-conserving surgery (BCS) followed by adjuvant radiotherapy has similar overall survival compared to mastectomybut is associated with higher rates of local recurrence. Positive surgical margins in BCS are the most important predictor of local recurrence. The aim of our study was to assess the risk factors associated with positive margins in women undergoing BCS for breast cancerin order to inform our clinical practice and minimize re-operation rates. Methods Patients with a diagnosis ofbreast cancer who underwent BCS from January 2013 to January 2021 were identified from our pathology database and included in the study. All patients underwent a lumpectomy with the removal of additional shaved cavity margins. Statistical analysis was used toassess the effect of patient clinical and pathological risk factors on the rate of positive margins. Results One hundred and twenty patients underwent BCS for breast cancer. Twenty-four percent of patients had positive margins. Of the 29 patients that underwent subsequent re-excisions, only 13 (45%) hadresidual disease in the re-excision specimen. In younger patients, tumors localized in lower quadrants and the presence of extensive intraductal component within invasive breast cancer increased the risk of positive margins. In addition, positive margins were encountered more significantly in patients with ductal carcinoma in situ (DCIS) compared to invasive tumors. Multivariate analysis showed that DCIS and young age were the only factors independently associated with positive margins. Conclusion DCIS and younger patients have a higher rate of positive margins during BCS than invasive breast cancer. For such patients at higher risk of positive margins, excision of cavity shave margins and intraoperative inking may be done to lower positive margin rates.Preoperative review of breast imaging, core biopsies, and counseling of patients about the likelihood of positive margins is important.

Non-Surgical Definitive Treatment for Operable Breast Cancer: Current Status and Future Prospects.

This article reviews the results of various non-surgical curative treatments for operable breast cancer. Radiotherapy is considered the most important among such treatments, but conventional radiotherapy alone and concurrent chemoradiotherapy do not achieve high cure rates. As a radiosensitization strategy, intratumoral injection of hydrogen peroxide before radiation has been investigated, and high local control rates (75-97%) were reported. The authors treated 45 patients with whole-breast radiotherapy, followed by stereotactic or intensity-modulated radiotherapy boost, with or without a radiosensitization strategy employing either hydrogen peroxide injection or hyperthermia plus oral tegafur-gimeracil-oteracil potassium. Stages were 0-I in 23 patients, II in 19, and III in 3. Clinical and cosmetic outcomes were good, with 5-year overall, progression-free, and local recurrence-free survival rates of 97, 86, and 88%, respectively. Trials of carbon ion radiotherapy are ongoing, with promising interim results. Radiofrequency ablation, focused ultrasound, and other image-guided ablation treatments yielded complete ablation rates of 20-100% (mostly ≥70%), but long-term cure rates remain unclear. In these treatments, combination with radiotherapy seems necessary to treat the extensive intraductal components. Non-surgical treatment of breast cancer is evolving steadily, with radiotherapy playing a major role. In the future, proton therapy with the ultra-high-dose-rate FLASH mode is expected to further improve outcomes.

Abstract P3-05-27: The impact of co-existing ductal carcinoma in situ in invasive early hormone receptor positive breast cancer on the genomic and clinical risk of recurrence

Abstract Background: Invasive early breast cancer (IBC) often presents with a co-existing ductal carcinoma in situ (DCIS) component, while about 5% of the cases present with an extensive (&amp;gt;25%) intraductal component (EIC). The presence of a DCIS component was previously shown to be associated with favorable clinico-pathological characteristics and survival outcomes. However, the association between co-existing DCIS and genomic risk of recurrence is unclear. Methods: Patients with early hormone receptor positive (HR+) HER2neu-negative (HER2-) breast cancer and known OncotypeDX breast recurrence score (RS), who underwent breast surgery in our institute, were included. A natural language processing (NLP) algorithm was used to identify co-existence of extensive DCIS (DCIS-H) and non-extensive DCIS (DCIS-L) in surgical pathological reports. Genomic risk was determined using OncotypeDX RS, while clinical risk was calculated according to the MINDACT criteria, based on tumor size and grade. The genomic and clinical risks of DCIS-H, DCIS-L and pure IBC (No-DCIS) were compared. Results: A total of 45 (5%) DCIS-H cases, 468 (56%) DCIS-L cases and 328 (39%) No-DCIS cases were identified. DCIS-H cases presented with less aggressive clinico-pathological characteristics, such as lower proportions of histologic grade III (10% vs 26% vs 21%) and lower proportions of node-positive disease (13% vs 18% vs 21%), compared to DCIS-L and No-DCIS cases, respectively. The distribution of OncotypeDX RS significantly varied between the groups. DCIS-H tumors were less likely to have a high RS and more likely to have a low or intermediate RS compared to DCIS-L and No-DCIS tumors (High RS: 4% vs 20% vs 20%, Low + intermediate RS: 96% vs 80% vs 80%, respectively; p=0.04). Additionally, the proportions of high clinical risk cases were lower in the DCIS-H group compared to the DCIS-L and No-DCIS groups (42% vs 53% vs 50%, respectively; p=0.002). Based on genomic and clinical risk and current guidelines, we found that women presented with an extensive DCIS component (DCIS-H) had a lower probability of receiving an adjuvant chemotherapy recommendation compared to women presented with a non-extensive DCIS component (DCIS-L) or pure IBC (No-DCIS) (11% vs 29% vs 25%, respectively; p=.035). No differences in disease recurrence were detected between the groups. Conclusions: Co-existing extensive DCIS in invasive early HR+Her2- breast cancer is significantly correlated with lower genomic and clinical risk of recurrence and a smaller chance for chemotherapy recommendation. The rarity of this condition (5% of cases) limited our ability to detect differences in outcomes. These findings warrant future studies of the underlying genomic landscape of co-existing extensive DCIS. Citation Format: Yael Bar, Kfir Bar, Judith Ben- Dror, Didi Feldman, Meishar Shahoha, Ahuva Weiss-Meilik, Nachum Dershowitz, Wolf Ido, Amir Sonnenblick. The impact of co-existing ductal carcinoma in situ in invasive early hormone receptor positive breast cancer on the genomic and clinical risk of recurrence [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-27.

Extensive Intraductal Component in Breast Cancer: What Role in Disease-Free Survival?

IntroductionExtensive intraductal component (EIC) associated to early breast cancer could increase the risk locoregional recurrence, but its impact on distant metastases is still unclear. The aim of the present study was to assess the role of EIC on 5-year survival outcomes in patients affected by early breast cancer treated with breast-conserving surgery. MethodsA total of 414 consecutive patients with a minimum follow-up of 60 mo were collected from January 2007 to December 2015. Disease-free survival (DFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival at 5 y were assessed considering the presence or absence of EIC and other clinical and pathological features. ResultsAbsence of EIC was independently associated with worse 5-year DFS (hazard ratio [HR] 1.68, P = 0.008) and 5-year DMFS (HR 1.93, P = 0.007), whereas 5-year locoregional recurrence-free survival was not affected (HR 1.50, P = 0.16). Five-year DFS was increased by EIC in T1 patients (P = 0.03) but not in T2 stage. Moreover, EIC was associated to better DFS in G2 (P = 0.03) and G3 patients (P = 0.01) but not in G1 cases. ConclusionsOur results suggest that EIC is independently correlated with increased 5-year DFS and in particular with 5-year DMFS.

Ten-year results of hypofractionated whole breast radiotherapy and intraoperative electron boost in premenopausal women

AimTo evaluate outcome of intraoperative electron boost (IOERT) and hypofractionated whole breast irradiation (HWBI) for breast cancer (BC) in young women. Methods and MaterialsWomen aged ≤ 48 with pT1-2 N0-1 BC received 12 Gy IOERT boost during conservative surgery followed by 3-dimensional conformal HWBI in 13 fractions (2.85 Gy/die). Local relapses (LR) and survival (disease-free, DFS; specific, BCSS; overall, OS) were analyzed. Results481 consecutive BC patients, mostly node negative, with median age of 42 were treated between 2004 and 2014. Median tumor size was 1.48 cm and median IOERT collimator was 4 cm. After 25-day mean interval, HWBI was delivered. At a median follow-up of 9.6 years, there were 23 LRs (4.8 %, 9 of which were in the boost region). Ten-year LR cumulative incidence was 4.1 % (95 %CI, 2.5–6.3). Over time, local control rate decreased for Luminal A and HER2 positive with negative hormonal receptors, while remained steady for triple negative. At multivariate analysis, LR predictors included age < 40, extensive intraductal component and the use of 4-cm IOERT collimator size. Ten-year survival outcomes were as follows: DFS 80.0 % (95 % CI, 75.8–83.5), BCSS 97.5 % (95 % CI, 95.5–98.6 %), OS 96.5 % (95 % CI, 94.3–97.9). Luminal B HER2 negative had the worse survival outcomes. Perioperative complications were uncommon (16.4 %), acute toxicity was mild (<2% Grade 3), but moderate/severe fibrosis was described in 40.8 % of the cases. Cosmesis was scored as excellent/good in 86 % of the cases. ConclusionsELIOT boost and HWBI achieved an excellent local control at the cost of tumor bed fibrosis. IOERT boost dose lower than 12 Gy is advisable.

The Accuracy of Mammography, Ultrasound, and Magnetic Resonance Imaging For the Measurement of Invasive Breast Cancer With Extensive Intraductal Components

BackgroundThe precise preoperative evaluation of radiologic tumor size with extensive intraductal component (EIC) is important. This study compared the accuracy of mammography, ultrasound (US), and magnetic resonance imaging (MRI) to measure invasive breast cancer with EIC. MethodsBetween 2007 and 2012, we collected data from 6816 patients who underwent surgery for invasive breast cancer at our institution. We reviewed the postoperative surgical reports of the tumors, in which the invasive tumor size and EIC were measured separately. Finally, we included 370 women who underwent preoperative mammography, US, and MRI. Each modality was retrospectively reviewed to measure the size of invasive breast cancer with EIC. The reference standard was surgical pathologic size and the accuracies of the image were evaluated. ResultsSpearman's correlation coefficient for the size of invasive cancer with EIC was good between MRI (r = 0.741) and pathology, and moderate between mammography (r = 0.661) or US (r = 0.514) and pathology. Both mass and nonmass lesions showed good correlations (intraclass correlation coefficient [ICC] = 0.672 and 0.612, respectively) in MRI. Furthermore, the subgroup of tumors without microcalcifications showed a higher correlation with MRI (ICC = 0.796) than with mammography (ICC = 0.620). However, the subgroup with microcalcifications showed a good correlation with mammography (ICC = 0.702) compared to MRI (ICC = 0.680) and US (ICC = 0.532). ConclusionThe lesion on mammography, US, and MRI reflected preoperative size of invasive cancer with EIC. MRI shows a higher correlation than mammography and US. However, cancer with calcifications of mammography shows a more accurate size than MRI or US.

AGO Recommendations for the Surgical Therapy of Breast Cancer: Update 2022.

The recommendations of the AGO Breast Committee on the surgical therapy of breast cancer were last updated in March 2022 (www.ago-online.de). Since surgical therapy is one of several partial steps in the treatment of breast cancer, extensive diagnostic and oncological expertise of a breast surgeon and good interdisciplinary cooperation with diagnostic radiologists is of great importance. The most important changes concern localization techniques, resection margins, axillary management in the neoadjuvant setting and the evaluation of the meshes in reconstructive surgery. Based on meta-analyses of randomized studies, the level of recommendation of an intraoperative breast ultrasound for the localization of non-palpable lesions was elevated to “++”. Thus, the technique is considered to be equivalent to wire localization, provided that it is a lesion which can be well represented by sonography, the surgeon has extensive experience in breast ultrasound and has access to a suitable ultrasound device during the operation. In invasive breast cancer, the aim is to reach negative resection margins (“no tumor on ink”), regardless of whether an extensive intraductal component is present or not. Oncoplastic operations can also replace a mastectomy in selected cases due to the large number of existing techniques, and are equivalent to segmental resection in terms of oncological safety at comparable rates of complications. Sentinel node excision is recommended for patients with cN0 status receiving neoadjuvant chemotherapy after completion of chemotherapy. Minimally invasive biopsy is recommended for initially suspect lymph nodes. After neoadjuvant chemotherapy, patients with initially 1 – 3 suspicious lymph nodes and a good response (ycN0) can receive the targeted axillary dissection and the axillary dissection as equivalent options.

Nipple-sparing Mastectomy with Immediate Implant-based Reconstruction for Patients with Pure Ductal Carcinoma in Situ.

The presence of an extensive intraductal component is associated to an increasing risk of relapse in the nipple-areola complex. The aim of the present study was to evaluate the outcomes of patients diagnosed with ductal carcinoma in situ (DCIS) who underwent nipple-sparing mastectomy (NSM) with immediate breast reconstruction using silicone implants. We retrospectively analyzed the postoperative complications and oncological safety of 67 breast cancer patients diagnosed with pure DCIS who underwent NSM with immediate breast reconstruction using silicone implants between 2004 and 2018. Among the 127 NSM procedures performed, 2 hematomas (1.5%) and 1 partial nipple necrosis (0.7%) were observed. After a mean follow-up of 60 months, the local recurrence rate was of 8.9%, the disease-free survival rate was of 90%, and 1 of the patients died. Despite the local recurrence rate, we showed that NSM with immediate breast reconstruction using silicone implants is a feasible surgical approach, with a low rate of complications and high survival rates for patients with a diagnosis of pure DCIS when breast-conserving surgery is not an option.

Evaluation of Breast Cancer Size Measurement by Computer-Aided Diagnosis (CAD) and a Radiologist on Breast MRI.

Purpose: This study aimed to evaluate cancer size measurement by computer-aided diagnosis (CAD) and radiologist on breast magnetic resonance imaging (MRI) relative to histopathology and to determine clinicopathologic and MRI factors that may affect measurements. Methods: Preoperative MRI of 208 breast cancers taken between January 2017 and March 2021 were included. We evaluated correlation between CAD-generated size and pathologic size as well as that between radiologist-measured size and pathologic size. We classified size discrepancies into accurate and inaccurate groups. For both CAD and radiologist, clinicopathologic and imaging factors were compared between accurate and inaccurate groups. Results: The mean sizes as predicted by CAD, radiologist and pathology were 2.66 ± 1.68 cm, 2.54 ± 1.68 cm, and 2.30 ± 1.61 cm, with significant difference (p < 0.001). Correlation coefficients of cancer size measurement by radiologist and CAD in reference to pathology were 0.898 and 0.823. Radiologist’s measurement was more accurate than CAD, with statistical significance (p < 0.001). CAD-generated measurement was significantly more inaccurate for cancers of larger pathologic size (>2 cm), in the presence of an extensive intraductal component (EIC), with positive progesterone receptor (PR), and of non-mass enhancement (p = 0.045, 0.045, 0.03 and 0.002). Radiologist-measured size was significantly more inaccurate for cancers in presence of an in situ component, EIC, positive human epidermal growth factor receptor 2 (HER2), and non-mass enhancement (p = 0.017, 0.008, 0.003 and <0.001). Conclusion: Breast cancer size measurement showed a very strong correlation between CAD and pathology and radiologist and pathology. Radiologist-measured size was significantly more accurate than CAD size. Cancer size measurement by CAD and radiologist can both be inaccurate for cancers with EIC or non-mass enhancement.

Abstract P4-07-04: Bc cancer ipsilateral breast tumor recurrence (BCC IBTR) nomogram

Abstract INTRODUCTION:. Local and systemic treatments for breast cancer have evolved in the past decades. This study reports the development of a modern population-based nomogram to individualize local recurrence (LR) risk estimates for patients treated with breast conservation surgery (BCS). The magnitude of benefit of adjuvant breast radiotherapy (BRT) depends on individual patient, tumor, and treatment characteristics (1). Nomograms can provide accurate predictions of LR and the absolute LR benefit of BRT that can assist patients in making informed decisions regarding BRT. This nomogram is based on a large cohort of women with prospectively captured biomarker data and modern systemic therapies including anti-human epidermal growth factor receptor 2 (HER2) therapy. METHOD:. Study Population:. The study cohort included women treated curatively for newly diagnosed breast cancer between 1st January 2005 and 31st December 2014. Inclusion criteria were: age &amp;gt;16 years, invasive ductal or lobular carcinoma, stage I-III, and BCS. Patients with metastatic disease, prior or synchronous contralateral breast cancer, unknown tumor or treatment characteristics, or treated with neoadjuvant therapy or mastectomy were excluded. Nomogram Development and Validation:. Age, tumor size, number of positive lymph nodes, grade, margin status, lymphovascular invasion (LVI), extensive intraductal component (EIC), estrogen receptor (ER), progesterone receptor (PR), HER2 status, use of chemotherapy, hormonal therapy, and radiotherapy with or without boost were recorded for each patient. The endpoint was LR as the first event. Fine and Gray’s competing risk model, with distant recurrence and death as competing risks, was used for the multivariable analysis, adjusting for demographics, tumor, and treatment factors. Hazard ratio (HR) and 95% confidence interval (CI) for each variable were calculated. The multivariable model forms the basis for the nomogram, which is being internally validated using the bootstrap and cross-validation. RESULTS:Of 11,310 patients, there were 429 LR (crude risk = 3.8%). The HR and 95% CIs from the Fine and Gray model for each of the variables in the nomogram are presented in the table. Age, number of positive nodes, grade, ER, LVI, margins, hormone therapy, chemotherapy, and radiotherapy were independent prognostic factors for LR. For patients treated with RT, the predicted 10-year cumulative incidence of LR ranged from 2.4% in patients with low-risk disease to 12.5% in patients with high-risk disease. CONCLUSION:A new nomogram for local recurrence, based on patients who had ER/PR/HER2 testing and who received modern systemic therapies is being developed. It will assist clinicians and patients individualize estimates of local recurrence risk and improve shared decision-making regarding the use of BRT in contemporary practice. REFERENCES:. (1)Sanghani, M., et al J Clin Oncol.,2010; 28(5), 718-722. Cox regression hazard ratios and confidence intervals for variablesCharacteristicHR95%CIp-valueAge0.980.970.99&amp;lt;0.01T-size1.011.001.010.14No. nodes1.041.011.070.005GradeGrade1---Grade21.751.322.33&amp;lt;0.001Grade32.541.813.56&amp;lt;0.001ERNeg---Pos1.441.012.060.046PRNeg---Pos0.790.611.030.084Her2Neg---Pos0.960.731.250.8LVINeg---Pos1.961.552.47&amp;lt;0.001Unk1.360.722.580.3Margin StatusNeg---Close1.411.081.840.011Pos1.681.082.590.200Extensive DCISNo---Yes1.140.841.550.4HTNo---Yes0.520.410.65&amp;lt;0.001ChemoNo---Yes0.540.420.71&amp;lt;0.001RTNo---Yes0.330.260.42&amp;lt;0.001BoostNo---Yes0.800.621.040.094 Citation Format: Dylan Narinesingh, Alan Nichol, Pauline Truong, Lovedeep Gondara, Caroline Speers, Laveniya Kugathasan, Caroline Lohrisch, Dave Voduc, Nafisha Lalani. Bc cancer ipsilateral breast tumor recurrence (BCC IBTR) nomogram [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-04.

Abstract P3-18-12: Achieving negative margin after repeated attempts for lumpectomy does not nullify the risk of ipsilateral breast tumor recurrences

Abstract Introduction: Currently, the widely accepted principle in managing lumpectomy margins in early breast cancer patients is to avoid the presence of tumor cell at the margin. The presence of tumor cells on lumpectomy margin can represent two different aspects of local control in breast cancer. One aspect is related to the potential technical failure that may lead to an incomplete resection of the tumor. The other aspect of positive margin is associated with a biologic nature of the tumor. For example, some tumors show features of extensive intraductal component which often result in positive lumpectomy margins and may lead to increased risk of local recurrence after breast conservation surgery. Therefore, the two-fold increase of IBTR risk with positive margin would be the reflection of the combined effect of both technical failure and the biologic features.In this study, we aimed to address this issue by investigating the IBTR rates of patients in whom negative margins were achieved by initial lumpectomy or by re-excision. Our assumption was if the IBTR rates of the two groups are identical, then the two-fold increase of IBTR risk is mostly caused by the technical incomplete resection and therefore the measures to achieve negative margins would be justified. Methods: We retrospectively reviewed the data of 5,633 patients who underwent breast conservation surgery and whole breast irradiation for invasive breast cancer between January 2004 and December 2018 from Seoul National University Hospital. During the period, a total of 828 patients had positive lumpectomy margin after their initial surgery. Among them, thirty-five patients who did not undergo re-operation were excluded due to the small sample size. Results: The median age of the studied patients was 49 years old (19-92), and nearly two third of the patients had T1 tumors (64.3%). 4,293 patients (76.7%) were node negative and 4,332 patients (77.4%) had hormone receptor positive tumors. During the median follow-up period of 76.6 ( ± 44.6) months, a total of 121 patients (2.2%) experienced IBTR. Patients who underwent re-excision to achieve negative margins experienced significantly higher rate of IBTR compared to patients in whom the margins were clear at the first lumpectomy (p=0.031, HR: 1.61; 95% C.I., 1.04-2.48). The survival curves began to separate around 4-5 years after surgery (98.5% vs 98.0% at 5 year and 97.4% vs 94.7% at 10 years of follow-up). The survival difference was more clearly observed for younger patients (p=0.033, HR 1.72; 95% C.I., 1.04-2.85 for age less than 50). When the patients were divided according to their hormone receptor and HER2 amplification status, we observed significant difference in HR+/HER2- and HR-/HER2- subtypes while the HER2-amplified tumors showed no significant differences.By using Cox regression analysis, we adjusted for other significant predictors of IBTR such as age, histologic grade, lymphovascular invasion, hormone receptor status, HER2 amplification status, and Ki-67 levels. The results of the Cox regression analysis showed that re-excision to achieve negative margin is significantly associated with the risk of IBTR after adjusting for these variables (p=0.023, HR: 1.72; 95% C.I., 1.08-2.74). Conclusion: Patients who underwent re-excision after lumpectomy for initial positive margin carry increased risk of developing IBTR even they achieve final negative margin when compared to patients with initially negative lumpectomy margin. Our observation indicate that a substantial proportion of the increasing risk of IBTR associated with positive lumpectomy margin can be attributed to the biologic characteristics of the tumor rather than technical incomplete resection. Citation Format: Jong Ho Cheun, Hong-Kyu Kim, Han-Byoel Lee, Wonshik Han, Hyeong-Gon Moon. Achieving negative margin after repeated attempts for lumpectomy does not nullify the risk of ipsilateral breast tumor recurrences [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-18-12.

Predictive value of ductal carcinoma in situ with invasive breast cancer in core needle biopsies for final pathologic size of intraductal elements

Preoperative evaluations of the size of ductal carcinoma in situ (DCIS) extension in invasive breast cancer (IBC) are problematic and markers of the actual size of DCIS remain elusive. This study aimed to quantify DCIS on core needle biopsy (CNB) and investigated its association with degree of DCIS extension on paired resection specimens, instead of with presence or absence of an extensive intraductal component or margin status as in earlier studies. This series examined 150 IBCs diagnosed from paired CNB and resection specimens. The DCIS/invasion ratio was calculated using the sum of each element size from CNB. In resection specimens, cases in which the greatest dimension of DCIS extension was longer than the greatest dimension of invasive size were defined as extended DCIS (Ext-DCIS). DCIS/invasion ratio level correlated positively with the degree of Ext-DCIS (P = 0.003). Using receiver operating characteristic curve analysis, setting cases with the subgroup of DCIS extension with greatest dimension > 2.5 times that of the invasive size in the resection specimen (Ext-DCIS > 2.5) as the positive class provided the best discrimination ability for DCIS/invasion ratio (0.375). In multivariate analysis, DCIS/invasion ratio > 0.375 was significantly associated with Ext-DCIS > 2.5 (P = 0.033). In conclusion, DCIS/invasion ratio > 0.375 in CNB was identified as a predictor of Ext-DCIS > 2.5 in resection specimens, suggesting that an approach combining DCIS/invasion ratio from CNB with preoperative staging may better predict the extent of DCIS and facilitate better surgical planning.