Stage Invasive Breast Cancer Research Articles

Abstract PO2-07-09: Early stage invasive lobular breast cancer is underestimated on conventional imaging including MRI

Abstract Background: Invasive lobular carcinoma (ILC), representing 15% of all invasive breast cancers, is characterized by loss or dysfunction of the adhesion molecule E-cadherin. This leads to an infiltrative growth pattern that is unlikely to disrupt the normal architecture of breast tissue. As a result, ILC is often non-mass forming and imaging is limited in correctly diagnosing stage I-III ILC. Mammography is believed to underestimate ILC, while MRI tends to overestimate the extent of ILC. The aim of this retrospective study was to correlate radiological with pathological findings. Methods: All patients diagnosed with stage I-III pure (i.e. not mixed) ILC between January 2000 and December 2020 who underwent primary surgery in University Hospitals Leuven, were included. Data on patient characteristics, preoperative imaging and pathology were collected from the patient files. Imaging and pathology measurements were compared by use of Pearson correlation coefficient, Whitney U test or Chi-square test. Weighted kappa statistics were used to assess agreement. Since the techniques of mammography and ultrasound have evolved in the past 20 years, different time periods were considered in sub-analyses (2000-2004, 2005-2009, 2010-2014, 2015-2020). Results: In total 1029 patients were included. Median age at diagnosis was 61.0 years (range 32.0 – 95.0 years). The breast density score determined on mammogram was Bi-RADS type A for 52 (5.1%) patients, B for 238 (23.1%) patients, C for 235 (22.8%) patients and D for 141 (13.7%) patients. Density score was missing from the reports of the remaining patients (n=363, 35.3%). Contrast enhanced breast magnetic resonance imaging (MRI) was performed in 709 (68.9%) patients. An increase in preoperative use of MRI was seen over the years. In comparison to tumor size reported by pathology, all imaging techniques underestimated the tumor size. The mean difference in largest tumor size compared to pathology was 14.64 ± 21.15 mm for mammography, 18.19 ± 21.66 mm for ultrasound and 9.93 ± 20.63 mm for MRI. A higher breast density level and a larger tumor size were significantly associated with a larger difference between diameter on pathology versus mammography (ρ=0.102, p-value 0.025 and ρ=0.530, p-value < 0.001 respectively). Changes over different time periods are shown in Table 1 for mammography and ultrasound. There was an agreement on unifocality versus multifocality between pathology and mammography for 81.2% of the patients. In 52.1% of the 236 cases where multifocality was reported on MRI, only 1 lesion was reported by the pathologist. Multifocality was seen on pathology in 12.0% of the 460 cases that were seen as unifocal lesions on MRI. Considering adenopathies, the false positive rate of ultrasound was 3.0%. However, the false negative rate was 68.3%. Conclusions: The local extent of ILC is underestimated by conventional imaging techniques. Unlike previous reports, our results suggest that tumor size of ILC is also underestimated by MRI. Ultrasound was inferior to mammography and MRI in estimating tumor size in our series. It was confirmed that MRI tends to overestimate the number of foci which might lead to unnecessary secondary ultrasounds and biopsies. The presurgical underestimation of lymph node involvement might increase the need of secondary surgeries. It is crucial to address these limitations in imaging of ILC and to prioritize the development of enhanced imaging techniques to improve diagnostic accuracy for these patients. Table 1: difference between imaging techniques and pathology by year of diagnosis Citation Format: Kaat Van Herck, Karen Van Baelen, Chantal Van Ongeval, Valerie Celis, Helen De Boodt, Machteld Keupers, Renate Prevos, Giuseppe Floris, Ines Nevelsteen, Ann Smeets, Thaïs Baert, Sileny Han, Hans Wildiers, Annouschka Laenen, Christine Desmedt, Patrick Neven. Early stage invasive lobular breast cancer is underestimated on conventional imaging including MRI [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 PO2-07-09.

Investigation of correlation between shear wave elastography and lymphangiogenesis in invasive breast cancer and diagnosis of axillary lymph node metastasis

BackgroundAccurate evaluation of axillary lymph node metastasis (LNM) in breast cancer is very important. A large number of hyperplastic and dilated lymphangiogenesis cases can usually be found in the pericancerous tissue of breast cancer to promote the occurrence of tumor metastasis.Shear wave elastography (SWE) can be used as an important means for evaluating pericancerous stiffness. We determined the stiffness of the pericancerous by SWE to diagnose LNM and lymphangiogenesis in invasive breast cancer (IBC).MethodsPatients with clinical T1-T2 stage IBC who received surgical treatment in our hospital from June 2020 to December 2020 were retrospectively enrolled. A total of 299 patients were eventually included in the preliminary study, which included an investigation of clinicopathological features, ultrasonic characteristics, and SWE parameters. Multivariable logistic regression analysis was used to establish diagnostic model and evaluated its diagnostic performance of LNM. The correlation among SWE values, collagen volume fraction (CVF), and microlymphatic density (MLD) in primary breast cancer lesions was analyzed in another 97 patients.ResultsThe logistic regression model is Logit(P)=-1.878 + 0.992*LVI-2.010*posterior feature enhancement + 1.230*posterior feature shadowing + 0.102*posterior feature combined pattern + 0.009*Emax. The optimum cutoff value of the logistic regression model was 0.365, and the AUC (95% CI) was 0.697 (0.636–0.758); the sensitivity (70.7 vs. 54.3), positive predictive value (PPV) (54.0 vs. 50.8), negative predictive value (NPV) (76.9 vs. 69.7), and accuracy (65.2 vs. 61.9) were all higher than Emax. There was no correlation between the SWE parameters and MLD in primary breast cancer lesions.ConclusionsThe logistic regression model can help us to determine LNM, thus providing more imaging basis for the selection of preoperative treatment. The SWE parameter of the primary breast cancer lesion cannot reflect the peritumoral lymphangiogenesis, and we still need to find a new ultrasonic imaging method.

Validation of primary and outcome data quality in a Swedish population-based breast cancer quality registry

BackgroundPopulation-based cancer quality registries are of great importance for the improvement of cancer care. However, little is known about the quality of recurrence data in cancer quality registries. The aim of this study was to evaluate data quality in the regional Breast Cancer Quality Registry of Central Sweden, with emphasis on the validity of recorded information on recurrence.MethodsValidation by re-abstraction was performed on a random sample of 800 women with primary invasive breast cancer stage I-III diagnosed between 1993 and 2010, of which 400 had at least one registered recurrence and 400 had no registered recurrence. Registry data were compared with data from medical records. Exact agreement, correlation and kappa values, sensitivity and specificity were calculated.ResultsSeven hundred forty-seven women (93%) were available for analysis. Exact agreement was high for diagnostics, tumor characteristics, surgery, and adjuvant oncological treatment (90% or more for most variables). The registry’s sensitivity was low for regional recurrence (47%), but higher for local and distant recurrence (80% and 75%), whereas specificity was overall high (≥ 95%). Combining all recurrence categories irrespective of localization improved sensitivity to 90% with a specificity of 91%. In 87% of women, the date of first recurrence according to medical records fell within ± 90 days of the date recorded in the registry.ConclusionsWhile the quality of data in the regional Breast Cancer Quality Registry was generally high, data accuracy on recurrences was lower. The overall precision of identifying any recurrence, irrespective of localization, was high. However, the accuracy of classification of recurrences (local, regional or distant) was lower, with evidence of underreporting for each of the recurrence categories. Given the importance of recurrence-related outcomes in the assessment of quality of care, efforts should be made to improve the reporting of recurrences.

Assignment of the biological value of solid breast masses based on quantitative evaluations of spectral CT examinations using electron density mapping, Zeffective mapping and iodine mapping

ObjectiveWe aimed to asses, in a clinical setting, whether the newly available quantitative evaluation of electron density (ED) in spectral CT examinations of the breast provide information on the biological identity of solid breast masses and whether ED maps yield added value to the diagnostic information of iodine maps and Zeff maps calculated from the same CT image datasets. MethodsAll patients at the University Breast Cancer Center who underwent a clinically indicated Dual Layer Computed Tomography (DLCT) examination for staging of invasive breast cancer from 2018 to 2020 were prospectively included. Iodine concentration maps, Zeff maps and ED maps were automatically reconstructed from the DLCT datasets. Region of interest (ROI) based evaluations in the breast target lesions and in the aorta were performed semi-automatically in identical anatomical positions using dedicated evaluation software. Case-by-case evaluations were carried independently by 2 of 4 radiologists for each examination, respectively. Statistical analysis derived from the ROIs was done by calculating ROC/AUC curves and Youden indices. ResultsThe evaluations comprised 166 DLCT examinations. In the ED maps the measurements in the breast target lesions yielded Youden cutpoints of 104.0% (reader 1) and 103.8% (reader 2) resulting in AUCs of 0.63 and 0.67 at the empirical cutpoints. The variables “Zeff” and “iodine content” derived from the target lesions showed superior diagnostical results, with a Youden cutpoint of 8.0 mg/ml in the iodine maps and cutpoints of 1.1/1.2 in the Zeff maps the AUCs ranging from 0.84 to 0.85 (p = 0.023 to <0.000). The computational combination of Zeff and ED measurements in the target lesions yielded a slight AUC increase (readers 1: 0.85–0.87; readers 2: 0.84–0.94). The ratios of the measured values in the target lesions normalized to the values measured in the aorta showed comparable results. The AUCs of ED derived from the cutpoints showed inferior results to those derived from the Zeff maps and iodine maps (ED: 0.64 and 0.66 for reader 1 and 2; Zeff: 0.86 for both readers; iodine content: 0.89 and 0.86 for reader 1 and 2, respectively). The computational combination of the ED results and the Zeff measurements did not lead to a clinically relevant diagnostic gain with AUCs ranging from 0.86 to 0.88. ConclusionsQuantitative assessments of Zeff, iodine content and ED all targeting the physical and chemical aspects of iodine uptake in solid breast masses confirmed diagnostically robust cutpoints for the differentiation of benign and malignant findings (Zeff < 7.7, iodine content of <0.8 mg/ml). The evaluations of the ED did not indicate any added diagnostic value beyond the quantitative assessments of Zeff and iodine content. Further research is warranted to develop suitable clinical indications for the use of ED maps.

Tumor response to neoadjuvant chemotherapy in molecular breast cancer subtypes in Medellin, Colombia. Retrospective cohort study

To describe the frequency of clinical and pathological response in different molecular subtypes of breast cancer, in patients receiving prior neoadjuvant chemotherapy. Descriptive retrospective cohort. The study population consisted of women 18 years of age and older with a histological diagnosis of invasive breast cancer stages IIA, IIB, IIIA, IIIB and IIIC, with a classification by molecular subtypes, who had received prior neoadjuvant chemotherapy, seen at a high complexity clinic in Medellin (Colombia), between July 1, 2017, and July 30, 2019. We measured age clinical stage, histological characteristics, molecular classification, and complete clinical and pathological responses by molecular subtype. A descriptive analysis was conducted. Overall, 255 patients met the inclusion criteria. Mean age was 55.2 years; the clinical stages with the highest prevalence were IIIB (28.6 %) and IIB (26.3 %), and the most frequent by histologic grading were grades 3 (48.2 %) and 2 (37.3 %). Frequency by molecular types was as follows: luminal A (10.2 %), HER2-negative luminal B (39.6 %), triple-negative (23.1%), HER2-positive luminal B (13.7 %), and pure HER2 (13.3 %). Complete clinical response following chemotherapy, by molecular type, was as follows: luminal A (26.9 %), HER2-negative luminal B (37.6 %), HER2-positive luminal B (48.6 %), pure HER2 (41.2 %), triple-negative (45.8 %). Complete pathological response by molecular subtype was achieved in the luminal A (19.2 %), HER2-negative luminal B (32.7 %), HER2-positive luminal B (54.3 %), pure HER2 (50 %) and triple-negative (42.4 %) subtypes. In clinical practice, breast cancer classification by molecular subtypes is a means to approach the assess the to neoadjuvant chemotherapy. Prospective studies are needed in the region in order to determine the ability to predict overall and disease-free survival based on the complete pathologic response.

Abstract P5-03-15: Application of 21-gene Breast Recurrence Score® assay to evaluate prognosis and benefit of adjuvant chemotherapy in BRCA1 and BRCA2 pathogenic variant carriers with early stage, estrogen receptor positive breast cancer

Abstract Background: Minimal data exists for the utilization of the Oncotype Dx® assay specifically in breast cancers associated with BRCA1/2 pathogenic variants (PVs). It is unknown whether estrogen receptor positive (ER+) breast cancer associated with an inherited BRCA1 or BRCA2 (BRCA1/2) PV is more aggressive than disease seen in patients who do not carry an inherited PV, and whether there are differences between BRCA1 and BRCA2. In prostate cancer patients with inherited cancer predisposition due to a BRCA2 PV, more aggressive cancers are observed, which influences first-line treatment. Limited data exists for the optimal management of early stage ER+ breast cancer in BRCA1/2 PV carriers. Comparing Recurrence Score® (RS) results in ER+ breast cancer patients with an inherited BRCA1/2 PV (cases) versus matched patients who test negative for a PV in BRCA1/2 (controls) may inform whether biologically more aggressive breast cancer is seen in BRCA1/2 carriers and optimal treatment approaches. Methods: A retrospective case control study was performed to compare RS results in women with breast cancer with an inherited BRCA1/2 PV versus patients who tested negative for an inherited BRCA1/2 PV. Female breast cancer patients seen between 2005-2020 at NorthShore University Health System with ER+Her2- early stage invasive breast cancer with 0-3 lymph nodes who completed genetic testing for BRCA1/2 were eligible for enrollment. BRCA1/2 cases were defined as individuals with an inherited PV in BRCA1/2 and controls were negative for BRCA1/2 or other known breast cancer risk gene PVs tested. Subjects were excluded if they had neoadjuvant therapy (hormonal or cytotoxic chemotherapy). Eligible cases were matched to control patients by age, grade, and stage. The Recurrence Score result was obtained by chart review; if not previously evaluated, Oncotype Dx assay was performed by Exact Sciences. Statistical analysis of the primary outcome used the paired t-test to determine mean difference in RS results between BRCA1/2 PV carriers and patients negative for a PV in BRCA1/2 using a 1:1 matched pairs design. Results: A total of 46 matched cases and controls were analyzed. Median age was 50 with a range of 28-74. Of the cases, 18 had a BRCA1 PV and 28 had a BRCA2 PV. Cases and controls were well matched for age (&amp;gt; 50 and ≤ 50); race, grade, stage, and progesterone receptor status. As expected, a higher number of BRCA1/2 carriers were treated with mastectomy while more of the controls received breast-conserving surgery. Chemotherapy was utilized more frequently in the cases (67.4%) versus the controls (54.4%). The average RS result was higher in the cases (27) than the controls (21.3) by a mean difference of 5.7 (p = 0.0195). Using Oncotype Dx cutoffs of low &amp;lt; 18, intermediate 18-30 and high ≥ 31, a statistically significant difference in RS result was noted in the cases versus controls. For cases in the highest risk group (Oncotype Dx ≥ 31), only 20% of their matches also had a score in the highest risk group while 35% had a score in the lowest risk group. Subgroup analysis showed that the cases had the largest difference in RS result from their controls in premenopausal women (age ≤ 50), BRCA1 carriers, and the node negative population. Conclusion We present one of the largest data sets available to date of a well-matched cohort of cases and controls which shows that BRCA1/2 PV carriers are more likely to have a higher Recurrence Score result than their matched controls when matched for age, grade, and stage. These findings suggest ER+ breast cancer in BRCA1/2 PV carriers is biologically more aggressive. Further investigation is warranted to evaluate how this important finding impacts adjuvant therapy recommendations for BRCA1/2 PV carriers. Citation Format: Poornima Saha, Ashley Aller, Amanda Deliere, Peter Hulick, Katharine Yao, Kristine Kuchta, Megan Sullivan, Allison DePersia. Application of 21-gene Breast Recurrence Score® assay to evaluate prognosis and benefit of adjuvant chemotherapy in BRCA1 and BRCA2 pathogenic variant carriers with early stage, estrogen receptor positive breast cancer [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 P5-03-15.

Changes in the tumor oxygenation but not in the tumor volume and tumor vascularization reflect early response of breast cancer to neoadjuvant chemotherapy

BackgroundBreast cancer neoadjuvant chemotherapy (NACT) allows for assessing tumor sensitivity to systemic treatment, planning adjuvant treatment and follow-up. However, a sufficiently large number of patients fail to achieve the desired level of pathological tumor response while optimal early response assessment methods have not been established now. In our study, we simultaneously assessed the early chemotherapy-induced changes in the tumor volume by ultrasound (US), the tumor oxygenation by diffuse optical spectroscopy imaging (DOSI), and the state of the tumor vascular bed by Doppler US to elaborate the predictive criteria of breast tumor response to treatment.MethodsA total of 133 patients with a confirmed diagnosis of invasive breast cancer stage II to III admitted to NACT following definitive breast surgery were enrolled, of those 103 were included in the final analysis. Tumor oxygenation by DOSI, tumor volume by US, and tumor vascularization by Doppler US were determined before the first and second cycle of NACT. After NACT completion, patients underwent surgery followed by pathological examination and assessment of the pathological tumor response. On the basis of these, data regression predictive models were created.ResultsWe observed changes in all three parameters 3 weeks after the start of the treatment. However, a high predictive potential for early assessment of tumor sensitivity to NACT demonstrated only the level of oxygenation, ΔStO2, (ρ = 0.802, p ≤ 0.01). The regression model predicts the tumor response with a high probability of a correct conclusion (89.3%). The “Tumor volume” model and the “Vascularization index” model did not accurately predict the absence of a pathological tumor response to treatment (60.9% and 58.7%, respectively), while predicting a positive response to treatment was relatively better (78.9% and 75.4%, respectively).ConclusionsDiffuse optical spectroscopy imaging appeared to be a robust tool for early predicting breast cancer response to chemotherapy. It may help identify patients who need additional molecular genetic study of the tumor in order to find the source of resistance to treatment, as well as to correct the treatment regimen.

Dosimetric evaluation of cardiac and left anterior descending artery dose in patients with left-sided breast cancer treated by different techniques of hypofractionated adjuvant radiotherapy after breast conservative surgery

The aims: to dosimetrically evaluate the dose to the heart and left anterior descending artery in left-sided early breast cases using different techniques.&#x0D; Materials and methods: Prospective observational/analytical study done in cases of left-sided BCS referred for adjuvant RT in 54 patients. Patients who underwent left-sided BCS (breast conservative surgery), patients aged between 18- and 75 years performance status ECOG 0-2, histological confirmed DCIS, Invasive Breast Cancer-Stage 1, 2, 3, patients without any evidence of metastatic disease Irrespective of hormonal receptor and HER-2 neu status are included in the study.&#x0D; Results: All the 3 parameters for LAD showed the highest doses with 3DCRT and lowest with VMAT. Thus our study favoured VMAT (p&lt;0.01) as the planning technique to achieve the least doses of LAD. However, for the heart, there was no statistically significant difference between 3DCRT and IMRT (p=0.349) for the average mean dose (Gy). On the other hand, there was a statistically significant difference between 3DCRT Vs VMAT and IMRT Vs VMAT (95 % CI, p&lt;0.01), again favouring VMAT as the choice of planning technique. The average heart max dose(Gy) and average heart V20(%) showed statistically significant benefits with VMAT (p&lt;0.01). There was a statistically significant benefit (p&lt;0.000) with VMAT for both LV parameters. At the same time, there was a statistically significant benefit in terms of ipsilateral lung dose with VMAT(p&lt;0.000), the dose to the right lung, right breast and favoured 3DCRT (p&lt;0.01). PTV95 % (Gy) by 3DCRT, IMRT, and VMAT in our study is 41.01, 41.96, and 41.76, respectively. Though the difference between the 3 techniques seems meagre, there was a statistically significant difference (p&lt;0.012) favouring IMRT.&#x0D; Conclusion: We conclude that using the VMAT technique in radiotherapy for left-sided breast cancer can significantly reduce radiation doses to the heart and LAD, potentially reducing cardiac risk. For all patients, the cardiac doses are considerably decreased for all dose levels without compromising the dose coverage to PTV, which is an advantage over IMRT and 3DCRT

Breast Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

The therapeutic options for patients with noninvasive or invasive breast cancer are complex and varied. These NCCN Clinical Practice Guidelines for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of ductal carcinoma in situ and the workup and locoregional management of early stage invasive breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org.

Risk of heart failure with preserved versus reduced ejection fraction in women with breast cancer.

While clinical heart failure (HF) is recognized as an adverse effect from breast cancer (BC) treatment, sparse data exist on specific HF phenotypes in affected BC survivors. We examined risk of HF by left ventricular ejection fraction (LVEF) status in women with a history of BC. 14,804 women diagnosed with all stages of invasive BC from 2005 to 2013 and with no history of HF were matched 1:5 to 74,034 women without BC on birth year, race, and ethnicity. LVEF values were extracted from echocardiography studies within 30days before through 90days after the HF clinical encounter. HF was stratified into HF with preserved ejection fraction (HFpEF, LVEF ≥ 45%) and HF with reduced ejection fraction (HFrEF, LVEF < 45%). Cumulative incidence rates (CIRs) were estimated with competing risk of overall death. Hazard ratios (HR) were calculated by multivariable Cox proportional hazards regression. Mean time to HF diagnosis was 5.31years (range 0.03-13.03) in cases and 5.25years (range 0.01-12.94) in controls. 10-year CIRs were 1.2% and 0.9% for overall HF, 0.8% and 0.7% for HFpEF, and 0.4% and 0.2% for HFrEF in cases and controls, respectively. In fully adjusted models, an overall significant increased risk of HF in cases versus controls was observed (HR: 1.31, 95% CI 1.14, 1.51). The increased risk was seen for both HFrEF (HR: 1.59, 95% CI 1.22, 2.08) and HFpEF (HR: 1.22; 95% CI 1.03, 1.45). BC survivors experienced higher risk of HF compared with women without BC, and the risk persisted across LVEF phenotypes. Systematic cardio-oncology surveillance should be considered to mitigate this risk in BC patients.

Do Breast Cancer Patients Manage to Participate in an Outdoor, Tailored, Physical Activity Program during Adjuvant Breast Cancer Treatment, Independent of Health and Socio-Demographic Characteristics?

Exercise could reduce the side-effects of adjuvant breast cancer treatment; however, socio-demographic, health, and intervention conditions may affect patients’ adherence to interventions. This study aimed to examine adherence to a 12-month outdoor post-surgery exercise program among newly diagnosed breast cancer patients during adjuvant treatment, and to identify socio-demographic and health-related predictors. In total, 47 women with invasive breast cancer stage I–II or ductal/lobular carcinoma grade 3 were included pre-surgery and randomized two weeks post-surgery to exercise (2 × 60 min/week). Patient characteristics (body-mass index (BMI), socioeconomic status, comorbidity, physical activity, and maximal oxygen uptake (VO2max)) were recorded pre-surgery. Correlations between adherence and patient characteristics and statistics for between-group differences were performed. The mean age was 54.2 years, mean BMI 27.8 kg/m2, and 54.2% received chemotherapy. Completers had a mean adherence of 81%, independent of season. Withdrawals (23%) occurred after a mean of 6.5 weeks (0–24 weeks), they were suggestively older, had lower socioeconomic status and pre-surgery VO2max, and higher BMI. Household income was significantly lower among withdrawals. There were insignificant correlations between adherence and health conditions. High adherence is achievable in a Nordic outdoor physical exercise program in breast cancer patients during adjuvant treatment, including chemotherapy. Additional studies are needed to clarify follow-up needs in some groups.

Does Breast Cancer Subtype Impact Margin Status in Patients Undergoing Partial Mastectomy?

Molecular subtype in invasive breast cancer guides systemic therapy. It is unknown whether molecular subtype should also be considered to tailor surgical therapy. The present investigation was designed to evaluate whether breast cancer subtype impacted surgical margins in patients with invasive breast cancer stage I through III undergoing breast-conserving therapy. Data from 2 randomized trials evaluating cavity shave margins (CSM) on margin status in patients undergoing partial mastectomy (PM) were used for this analysis. Patients were included if invasive carcinoma was present in the PM specimen and data for all 3 receptors (ER, PR, and HER2) were known. Patients were classified as luminal if they were ER and/or PR positive; HER2 enriched if they were ER and PR negative but HER2 positive; and TN if they were negative for all 3 receptors. The impact of subtype on the margin status was evaluated at completion of standard PM, prior to randomization to CSM versus no CSM. Non-parametric statistical analyses were performed using SPSS Version 26. Molecular subtype was significantly correlated with race (P = .011), palpability (P = .007), and grade (P < .001). Subtype did not correlate with Hispanic ethnicity (P = .760) or lymphovascular invasion (P = .756). In this cohort, the overall positive margin rate was 33.7%. This did not vary based on molecular subtype (positive margin rate 33.7% for patients with luminal tumors vs 36.4% for those with TN tumors, P = .425). Molecular subtype does not predict margin status. Therefore, molecular subtype should not, independent of other factors, influence surgical decision-making.

Preliminary Results of Multi-Institutional Phase 1 Dose Escalation Trial Using Single-Fraction Stereotactic Partial Breast Irradiation for Early Stage Breast Cancer

We report on our early experience of our prospective multicenter phase 1 dose- escalation study of single-fraction stereotactic partial breast irradiation (S-PBI) for early stage breast cancer after partial mastectomy using a robotic stereotactic radiation system. Thirty women with in situ or invasive breast cancer stage 0, I, or II with tumor size <3 cm treated with lumpectomy were enrolled in this phase 1 single-fraction S-PBI dose-escalation trial. Women received either 22.5, 26.5, or 30 Gy in a single fraction using a robotic stereotactic radiation system. The primary outcome was to reach tumoricidal dose of 30 Gy in a single fraction to the lumpectomy cavity without exceeding the maximum tolerated dose. Secondary outcomes were to determine dose-limiting toxicity and cosmesis. Tertiary goals were ipsilateral breast recurrence rate, distant disease-free interval, recurrence-free survival, and overall survival. From June 2016 to January 2021, 11, 8, and 10 patients were treated to doses of 22.5, 26.5, or 30 Gy in a single fraction, respectively, with median follow-up being 47.9, 25.1, and 16.2 months. No patients experienced acute (<90 days) grade 3 or higher treatment-related toxicity, and maximum tolerated dose was not reached. There were 2 delayed grade 3 toxicities. Four patients (13.8%) developed fat necrosis across all 3 cohorts, which compares favorably with results from other PBI trials. No dose cohort had a statistically significant cosmetic detriment from baseline to 12 months or 24 months follow-up by patient- or physician-reported global cosmetic scores. There were no reports of disease recurrence. This phase 1 trial demonstrates that S-PBI can be used to safely escalate dose to 30 Gy in a single fraction with low toxicity and without detriment in cosmesis relative to baseline.

Impact of COVID-19 pandemic in 2020 on the diagnosis and management of breast cancer in Korea: A multi-institutional study.

10566 Background: Since the COVID-19 pandemic began in early 2020, there have been many reports that it has had a significant impact on screening, case identification and referral in cancer diagnosis. We investigated the diagnostic and therapeutic status of breast malignancy before and after the COVID-19 pandemic at the multi-institution level. Methods: We have reviewed the records of patients with breast cancer from February 2019 to July 2020 in six university hospitals in Korea. The patients were divided into two groups according to the initial date of cancer diagnosis: Period A, from February to April and Period B, from May to July in 2020. The two groups were compared for the same periods in 2019. The goals were to determine whether breast cancer screening and diagnosis have been delayed and thus resulted in stage migration. We also examined the difference in the number of surgeries in patients diagnosed with breast cancer during those periods. Results: The total of 1,669 breast malignancy diagnosis was made in the grouped periods of 2019, and 1,369 diagnoses in 2020. All patients were screened by PCR test for COVID-19 prior to hospitalization, and none of them tested positive. Overall, there was a 9.9% reduction in the number of diagnoses than in 2019 and the decrease was more significant in Period A (11.1% vs. 8.7%). According to the age, there was no difference until the 30s but decreased from those in their 40s and above. The decline was more pronounced in the elderly. The COVID-19 pandemic has affected breast cancer screening (decreased by 27.4%) and more diminished in Period A (41.0% vs. 19.0%). Invasive breast cancer stage was not statistically different in Period A compare with 2019 (p = 0.170). But the stage in Period B was different (p = 0.032), and more patients were observed in advanced stages in 2020. The decrease in surgery was noticeably observed in Period A (4.6%, from 480 to 438 surgeries) and not in Period B. The analysis of reconstruction surgery was similar. Conclusions: Patients with COVID-19 increased exponentially from late February in Korea. However, the number of patients per day decreased to less than 100 on March 15 and then flattened. The health care system for cancer was not overloaded and restrictions on visiting hospital were minimal. Analysis in the pandemic period of the 6-month showed that the number of breast cancer screening, diagnosis and surgeries decreased compared with the previous year. Those decreases were prominent in Period A when the COVID-19 patient surged. The upstage migration of breast cancer was generally insignificant but slightly occurred in Period B. The outbreak of infectious disease makes patients reluctant to come to the hospital, especially in the elderly. We need to discuss the potential long-lasting deleterious effect of the COVID-19 pandemic on cancer diagnosis and management. And we should prepare for how to deal with the backlog caused by the COVID-19 pandemic.

Abstract PS4-45: Computerized image analysis of nuclear morphological features reveals differences in phenotype and prognosis of disease free survival of early stage ER+ breast cancers for South Asian and North American women

Abstract Background: Breast cancer is the most common cancer worldwide. There has been emerging interest in studying differences in breast tumor phenotypes between South Asian and South American women given that racial/ethnic disparities in incidence and mortality have been demonstrated in multiple studies. South Asian women are more likely to be diagnosed with an advanced stage breast tumor despite lower incidence than in North American women. There is evidence that computer-extracted nuclear morphological features on H&amp;E slide images may be associated with breast cancer aggressiveness, specifically recurrence and disease free survival. However, studies have mostly focused on North American women. In this work, we evaluated whether there is a difference in computer extracted features of nuclear morphology from H&amp;E tissue slide images between South Asian (SA) and North American (NA) women and we also investigated how these differences could impact the development of population specific breast cancer prognostic models. Methods: H&amp;E slides of breast tumors from patients who were diagnosed with ER+ early stage invasive breast cancer from Tata Memorial Centre, India (SA: 69 (20 recurrence)) and from University Hospitals Cleveland Medical Center (NA: 121 (20 recurrence)), along with outcome information were collected. All slides were digitized on either a Ventana DP 200 or a Roche Ventana iScan HT slide scanner. For each image, a conditional Generative Adversarial Network model was employed to segment the individual nuclei, which were used to generate 241 nuclear features including nuclear architecture, shape, orientation disorder, and texture features. Half of the patients (95) were randomly selected as the training set (Stra) with the remaining patients as the hold-out validation set (Stest). Three elastic net regularized Cox regression models (MSA, MNA, MSA+NA) were trained fitting between the nuclear features and disease free survival (DFS) respectively for SA subset, NA subset, and SA &amp; NA set in Stra. The top five prognostic features were identified respectively from each of the three models (MSA, MNA, MSA+NA) which were further validated on Stest to evaluate their prognostic value in prediction of DFS. Results: We found that the prognostic features identified by MNA and MSA+NA were mostly shape features (three out of five for MNA, four out of five for MSA+NA), while the prognostic features identified by the model specifically trained with the SA population (MSA) were mostly texture features (three out of five), possibly reflecting chromatin patterns in the cell. MSA yielded a better performance (Hazard Ratio=4.99 (p=0.00928, CI=1.32-18.9) from log-rank test between model derived high and low risk categories) on SA population in Stest compared to MNA and MSA+NA. Conclusion: We found that nuclear histomorphometry features were different between breast cancer patients from South Asia and those from North America. The prognostic capability of the computational pathology-based models for South Asian women could be significantly improved by taking into account population-specific information. An additional independent validation set is needed to confirm the preliminary findings presented here. Citation Format: Haojia Li, Kaustav Bera, Paula Toro, Pingfu Fu, Vidya Rao, Shabina Siddique, Aparna Harbhajanka, Haley Sechrist, Zelin Zhang, Sangeeta Desai, Vani Parmar, Anant Madabhushi. Computerized image analysis of nuclear morphological features reveals differences in phenotype and prognosis of disease free survival of early stage ER+ breast cancers for South Asian and North American women [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 PS4-45.

Abstract PS7-89: The socioeconomic impact of breast cancer in Brazil: An analysis of AMAZONA III cohort study

Abstract INTRODUCTIONPatients diagnosed with breast cancer (BC) in Brazil are on average 54 years old and the majority (70%) have stage II-III. Age and clinical stage have a negative impact on patient personal life and labor productivity. The socioeconomic status is a fundamental part of the population’s health, which includes marital and employment status. Our aim was to analyze the socioeconomic impact of BC diagnosis which is poorly studied in low or middle-income countries. METHODSThis is a cross-sectional study including patients from AMAZONA III cohort study. Eligible patients were female aged &amp;gt; 18 years with diagnosis of any stage invasive BC from 2016 to 2018 in 24 participating hospitals in Brazil. The present analysis evaluated the marital and employment status at baseline and at 1-year follow-up after BC diagnosis. Patients with missing data were excluded and women older than 60 years, retirement age in Brazil, were not included in this analysis. A multivariate Poisson regression analysis with robust variance was adjusted to assess which patients’ characteristics associated with job loss and relationship status. The characteristics evaluated were age (⇐ 50 vs. &amp;gt; 50 years), educational level (Illiterate to completed first degree or completed second degree vs. higher), personal income (no income – 2 minimum wages vs. 2 to 5 minimum wages vs. more than 5 minimum wages), clinical-stage (I-III vs. IV), molecular subtype (luminal, HER2 positive vs. triple negative), surgery type (breast conserving surgery vs. any type of mastectomy), and systemic treatment (chemotherapy vs. hormonal therapy vs. none). The significance level was set at 5%. All analyses were conducted using SAS version 9.4 (SAS Institute, Cary, NC). RESULTSFrom a total of 1257 patients with evaluable employment status, 655 patients (52.1%) had working activity at the time of BC diagnosis. After 1 year of follow-up, there was an absolute decrease of 5.3% in patients’ employment (52.1% to 46.8%; p= 0.0075). Loss of employment was higher in older patient &amp;gt; 50 years (8.7%), lower educational level (9.9%), those earning 2-5 minimum wages (11.2%), stage I-III (7%), triple negative (6.9%), mastectomy (9.9%) and treatment with hormone therapy (11%). Patients with higher educational level (RR 0.61, 95% CI 0.36-0.94, p=0.0265) were at lower risk of employment loss whereas patients with personal income of more than 2 minimum wages (RR 1.83, 95% CI 1.08-3.10, p=0.0236) and mastectomy (RR 2.16, 95% CI 1.47-3.17, p=0.0015) were at higher risk of being unemployed loss after 1 year of diagnosis. Other factors such as age, clinical stage, BC subtype and treatment were not independently associated with unemployment. A total of 1947 patients had marital status information at baseline. Of those, 1182 (60.7%) were married or in common-law marriage at BC diagnosis. After 1 year of follow-up, 52 (2.7%) of these women loss their relationship (60.7% vs. 58%; p=0.08). Loss of relationships was higher (5.2%) in younger patients (≤ 50 years), lower educational level (4.9%), no income or up to 2 minimum wages (5.4%), stage IV (7.7%), HER2 positive (5.5%), mastectomy (5.4%) and treatment with hormone therapy (5.5%). None of the variables evaluated such as age, educational level, personal income, clinical-stage, molecular subtype, surgery type and systemic treatment, were significantly associated with change of marital status for patients previously married or in common-law marriage. CONCLUSION The socioeconomic impact of BC diagnosis was minimal at 1-year follow-up in Brazil. Nonetheless personal income and surgery type were associated with higher chance of unemployment whereas no specific variables were related to marital status change. Government social policies specifically for work return remains critical for BC patients in short-term after BC diagnosis. Citation Format: Gustavo Werutsky, Daniela Dornelles Rosa, Carlos Barrios, Eduardo Cronemberger, Geraldo Queiroz, Jose Bines, Mahira Lopes Rosa, Rafaela Gomes, Ana P Heck, Laura Freitas, Arthur F da Silva, Matheus Rodrigues, Andre P Fay, Sergio Simon. The socioeconomic impact of breast cancer in Brazil: An analysis of AMAZONA III cohort study [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 PS7-89.

Moving beyond the stage: how characteristics at diagnosis dictate treatment and treatment-related quality of life year losses for women with early stage invasive breast cancer

ABSTRACT Background:Although evaluations of breast cancer screening programs frequently estimate quality-adjusted life-year (QALY) losses by stage, other breast cancer characteristics influence treatment and vary by mode of detection – i.e. whether the cancer is detected through screening (screen-detected), between screening rounds (interval-detected) or outside screening (community-detected). Here, we estimate the association between early-stage invasive breast cancer (ESIBC) characteristics and treatment-related QALY losses. Methods:Using clinicopathological and treatment information from 675 women managed for ESIBC, we estimated the average five-year treatment-related QALY loss by detection group. We then used regression analysis to estimate the extent to which known cancer characteristics and the detection mode, are associated with treatment and treatment-related QALY losses. Results:Community-detected cancers had the largest QALY loss (0.76 QALYs [95% CI 0.73;0.80]), followed by interval-detected cancers (0.75 QALYs [95% CI 0.68;0.82]) and screen-detected cancers (0.69 QALYs [95%CI 0.67;0.71]). Adverse prognostic factors more common in community-detected and interval-detected breast cancers (large tumours, lymph node involvement, high grade) were largely associated with QALY losses from mastectomies and chemotherapy. Receptor-positive subtypes, more common in screen-detected cancers, were associated with QALY losses related to endocrine therapy. Conclusions:The associations between ESIBC characteristics and treatment-related QALY losses should be considered when evaluating breast cancer screening and treatment strategies.

Cosmetic Outcomes of a Phase 1 Dose Escalation Study of 5-Fraction Stereotactic Partial Breast Irradiation for Early Stage Breast Cancer

Our purpose was to evaluate cosmetic changes after 5-fraction adjuvant stereotactic partial breast irradiation (S-PBI). Seventy-five women with in situ or invasive breast cancer stage 0, I, or II, with tumor size ≤3 cm, were enrolled after lumpectomy in a phase 1 dose escalation trial of S-PBI into cohorts receiving 30, 32.5, 35, 37.5, or 40 Gy in 5 fractions. Before S-PBI, 3 to 4 gold fiducial markers were placed in the lumpectomy cavity for tracking with the Synchrony respiratory tracking system. S-PBI was delivered with a CyberKnife robotic radiosurgery system. Patients and physicians evaluated global cosmesis using the Harvard Breast Cosmesis Scale. Eight independent panelists evaluated digital photography for global cosmesis and 10 subdomains at baseline and follow-up. McNemar tests were used to evaluate change in cosmesis, graded as excellent/good or fair/poor, from baseline to year 3. Wilcoxon signed rank tests were used to evaluate change in subdomains. Cohen's kappa (κ) statistic was used to estimate interobserver agreement (IOA) between raters, and Fleiss' κ was used to estimate IOA between panelists. Median cosmetic follow-up was 5, 5, 5, 4, and 3 years for the 30, 32.5, 35, 37.5, and 40 Gy cohorts. Most patients reported excellent/good cosmesis at both baseline (86.3%) and year 3 (89.8%). No dose cohort had significantly worsened cosmesis by year 3 on McNemar analysis. No cosmetic subdomain had significant worsening by year 3. IOA was fair for patient-physician (κ = 0.300, P < .001), patient-panel (κ = 0.295, P < .001), physician-panel (κ = 0.256, P < .001), and individual panelists (Fleiss κ = 0.327, P < .001). Dose escalation of S-PBI from 30 to 40 Gy in 5 fractions for early stage breast cancer was not associated with a detectable change in cosmesis by year 3. S-PBI is a promising modality for treatment of early stage breast cancer.

Increasing Mortality in Korean Patients With Breast Cancer: High Mortality Rate in Elderly Breast Cancer Population Due to Suboptimal Treatment and Other Diseases.

BackgroundThe incidence of breast cancer in Asia, including Korea, has rapidly increased. Each country has shown different clinical features. This study presents a comprehensive understanding of breast cancer in different age groups in Korea and determines potential measures for improving patient survival.MethodsPatients diagnosed with invasive breast cancer stages I to III with available clinicopathologic and follow-up data were included in the study. Kaplan–Meier survival graphs were generated for each group and compared using log-rank test. The hazard ratio for each risk factor was calculated using the Cox regression model and the 95% confidence interval.ResultsThe final cohort included 833 patients with a mean age of 51.3±11.3 years (range, 22–89 years), and 191 (22.9%) of them were aged >60 years. Patients aged ≥60 years had worse overall survival (OS) and distant disease-free survival than those aged <60 years. Although no difference was observed in the tumor biology, elderly patients showed significant differences in practice patterns: they tended to undergo mastectomy (40.2% vs 62.8%, P<0.001), did not receive the standard chemotherapy (88.4% vs 69.3%, P < 0.001), and had a higher risk of developing second primary cancer or diseases other than breast cancer (1.2% vs 6.8%, P < 0.001), which significantly correlated with poor survival in elderly patients.ConclusionLess-than-the-standard treatment of care or development of a second primary disease resulted in poor prognosis in elderly patients in Korea. A multi-institutional and multinational study is warranted to elucidate the clinical features of breast cancer in Asian patients.

Effects of a 1-Year Physical Activity Intervention on Markers of Hemostasis among Breast Cancer Survivors: A Randomized Controlled Trial.

Introduction Physical activity may reduce the development of breast cancer. Whereas hypercoagulability has been linked to adverse outcomes in breast cancer patients, the effects of physical activity on their hemostatic factors are unknown. The study aimed to assess whether long-term (1 year) physical activity can affect hemostatic factors in breast cancer patients. Methods Fifty-five women (35–75 years) with invasive breast cancer stage I/II were randomized to a physical activity intervention ( n = 29) lasting 1 year or to a control group ( n = 26), and analyzed as intention to treat. Fibrinogen, factor VII antigen, tissue factor pathway inhibitor, and von Willebrand factor (VWF) antigen as well as prothrombin fragment 1 + 2, the endogenous thrombin potential and D-dimer, were measured in plasma before intervention (baseline), and then after 6 and 12 months. Results Maximal oxygen uptake (measure of cardiorespiratory fitness) decreased the first 6 months among the controls, but remained stable in the intervention group. We found no significant differences between the two study groups regarding any of the hemostatic factors, except a significantly higher increase in factor VII antigen in the intervention group. The effect of the intervention on VWF was, however, significantly affected by menopausal stage, and a significant effect of the intervention was found on VWF among postmenopausal women, even after adjustment for dietary intake. Conclusion Long-term physical activity had no effect on the majority of the hemostatic factors measured, but led to increased plasma concentrations of factor VII antigen and prevented an increase in VWF concentration after breast cancer treatment in postmenopausal women. The clinical impact of these findings for risk of vascular thrombosis warrants further studies.