Ductal Carcinoma In Situ Patients Research Articles

Longitudinal assessment of real-world patient adherence: a 12-month electronic patient-reported outcomes follow-up of women with early breast cancer undergoing treatment

BackgroundElectronic patient-reported outcomes (ePROs) assess patients’ health status and quality of life, improving patient care and treatment effects, yet little is known about their use and adherence in routine patient care.AimsWe evaluated the adherence of invasive breast cancer and ductal carcinoma in situ (DCIS) patients to ePROs follow-up and whether specific patient characteristics are related to longitudinal non-adherence.MethodsSince November 2016, the Breast Center at Charité – Universitätsmedizin Berlin has implemented an ongoing prospective PRO routine program, requiring patients to complete ePROs assessments and consent to email-based follow-up in the first 12 months after therapy starts. Frequencies and summary statistics are presented. Multiple logistic regression models were performed to determine an association between patient characteristics and non-adherence.ResultsOut of 578 patients, 239 patients (41.3%, 95%CI: 37.3–45.5%) completed baseline assessment and all five ePROs follow-up during the first 12 months after therapy. On average, above 70% of those patients responded to the ePROs follow-up assessment. Adherence to the ePROs follow-up was higher during the COVID-19 pandemic than in the time periods before (47.4% (111/234) vs. 33.6% (71/211)). Factors associated with longitudinal non-adherence were younger age, a higher number of comorbidities, no chemotherapy, and a low physical functioning score in the EORTC QLQ-C30 at baseline.ConclusionsThe study reveals moderate adherence to 12-month ePROs follow-up assessments in invasive early breast cancer and DCIS patients, with response rates ranging from 60 to 80%. Emphasizing the benefits for young patients and those with high disease burdens might further increase adherence.

Abstract PS01-06: The relationship between margin status of <2mm and local recurrence in DCIS patients

Abstract Background: There has been controversial evidence regarding adequate margin in breast conserving surgery (BCS) for ductal carcinoma in situ (DCIS). However, the consensus is a surgical margin distance of 2 mm. Moreover, recent recommendations advised on ‘’clinical judgement’’ approach to re-excision in cases of margin distance < 2mm. The ongoing controversy in DCIS margin compared to invasive cancer margin is due to the differences in post operative management. This is important as margin status is one of the modifiable risk factor for local regional recurrence in DCIS. In our study we evaluated margin distance in patient diagnosed with DCIS who underwent BCS on local recurrence Methods: Patients who underwent breast conserving surgery between February 2000 and December 2018 at Asan Medical Center were retrospectively reviewed. Patients with involved resection margins were excluded. Kaplan-Meier survival analysis and Cox proportional hazard models were applied to determine the relationship between negative margin width and local recurrence. Results: A total of 1,858 patients were included in the study. Almost half of the patients had a tumor size of 1cm or smaller (n=876, 47.1%). Only 98 (5.3%) patients did not undergo radiation therapy. A negative margin width of < 1mm, < 2mm, < 5mm were all not associated with local recurrence (log-rank test p-value 0.1, 0.1, 0.078, respectively). For patients who underwent radiation therapy, a negative margin of any width was not related to local recurrence. Whereas, for patients who did not undergo radiation therapy, those with margins ≤2mm were significantly more likely to develop local recurrence than those with margins < 2mm (10-yr local recurrence rate, 16.4% vs 5.5%, respectively; hazard ratio, 5.709; 95% CI, 1.106-29.46, p=0.038). Conclusion: A negative margin is not related to local recurrence in DCIS patients who undergo breast conserving surgery with radiation therapy. Routine additional surgery for wider negative margin may only be needed for patients who do not undergo radiation therapy. Citation Format: Sarah Al Safi, Tae-Kyung Yoo, Sae Byul Lee, Jisun Kim, Il-Yong Chung, Hee Jeong Kim, Beom Seok Ko, Jong Won Lee, Byung Ho Son, Hee Jin Lee, Gyungyub Gong. The relationship between margin status of <2mm and local recurrence in DCIS patients [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 PS01-06.

Abstract PO5-01-01: The comparison of HER2 low and HER2 0 in ductal carcinoma in situ (DCIS) for breast cancer

Abstract Background: Trastuzumab deruxtecan is a standard of care after prior chemotherapy for metastatic breast cancer with HER2 low. HER2 low recognized as a new category of breast cancer. The definition of HER2 low is IHC 1+ or IHC 2+/ISH- in invasive ductal components. We have already reported the frequency and prognosis of HER2 positive and low in invasive cancer (Breast Cancer. 2022;29:234-241), but the distribution and characteristics of HER2 low in ductal carcinoma in situ (DCIS) is unknown. It is also well known that HER2 expression is higher in DCIS than in invasive cancer. We focused on the frequency of HER2 low in DCIS, performed an analysis of its frequency and characteristics, and compared to DCIS with HER2 0. Methods: We retrospectively examined breast cancer patients with DCIS and invasive ductal carcinoma (IDC) who underwent surgery at our institution between 2005 and 2015. Regarding the expression status of HER2, we classified cases into three groups: HER2 0, HER2-low (defined as IHC 1+ or IHC 2+/ISH-), and HER2-positive (IHC 2+/ISH+ or IHC 3+), and investigated their frequency. We analyzed the relationship between HER2 expression and Van Nuys classification, as well as the relationship between HER2 expression and ER expression, using the chi-square test. Results: A total of 726 DCIS patients were included in this analysis. The patient demographics showed a median age of 52 years (range: 20-84), with 413 patients (56.9%) undergoing total mastectomy and 311 patients (42.8%) undergoing breast-conserving surgery (two cases had unknown surgical procedures). The expression of HER2 in DCIS patients was observed as HER2-0, low and positive in 100 (13.8%), 474 (65.3%) and 152 patients (20.9%), respectively. The expression of HER2 in IDC was observed as HER2 0, low and positive in 838 (17.1%), 3169 patients (64.4%) and 911 patients (18.5%) (Table 1). DCIS tended to have higher HER2 expression(P=0.048). Then we compared the characteristics of HER2 0 and HER2 low in DCIS. Table 2 shows the relation between Van Nuys classification and HER2 expression. Van Nuys classification was evaluated in 346 cases. Van Nuy grade 3 accounted for 4.8% of the HER2 0 cases and 15.8% of the HER2 low cases. HER2 low cases tend to have higher grades(P < 0.01). Table 3 shows the relation between ER expression and HER2 expression. ER negative accounted for 5% of HER2 0 cases and 8.4% of HER2 low cases. ER negatives tended to be more common in Her2 low cases(P < 0.01). Conclusion: HER2 low is not considered a molecular biological classification, but rather a classification of the target of treatment for Trastuzumab deruxtecan. In our study, comparing HER2 0 and HER2 low, HER2 low tended to have higher grade and lower ER expression. Further investigation including basic research is needed to clarify the biological meaning of her2 low. Table1: The frequency of HER2 expression in DCIS and IDC Table2: The relationship between Van Nuys classification and HER2 expression Table3: The relationship between ER status and HER2 expression Citation Format: Nari Kureyama, Maho Kusudo, Akira Nakakami, Rie Komaki, Yuka Endo, Kazuki Nozawa, Ayumi Kataoka, Haruru Kotani, Akiyo Yoshimura, Masaya Hattori, Masataka Sawaki, Hiroji Iwata. The comparison of HER2 low and HER2 0 in ductal carcinoma in situ (DCIS) for 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 PO5-01-01.

Abstract GS03-01: Magnetic Resonance Imaging and a 12-Gene Expression Assay to Optimize Local Therapy for Ductal Carcinoma In Situ: 5-year clinical outcomes of E4112

Abstract BACKGROUND. Advanced diagnostics such as magnetic resonance imaging (MRI) and gene-expression profiles are potentially useful to guide treatment in patients with ductal carcinoma in situ (DCIS). To evaluate these tests, we performed a prospective single arm multicenter study. We have previously reported the impact of MRI on surgical management of DCIS patients, and the effect of a 12-gene DCIS Score (DS) on radiotherapy (RT) use after wide local excision (WLE). We now report a pre-planned analysis of ipsilateral breast events (IBE) at 5-years. METHODS. Adult women with a core needle biopsy diagnosis of DCIS and eligible for WLE based on conventional imaging were registered following consent. All registered patients underwent breast MRI. Those still eligible, and willing, to receive WLE after appropriate follow-up biopsies underwent resection to free margins. DCIS sections were submitted to Exact Sciences for DS. Those with a low DS (< 39) were advised to omit RT; those with intermediate/high (inter/hi) DS (≥39) were advised to receive RT. All participants were monitored at 6-month intervals for any breast cancer event, and for survival. An IBE was defined as the first DCIS or invasive recurrence in the ipsilateral breast following the final WLE. Participants without IBE were censored by date of last contact or date of death for those who died. Follow-up was truncated at 5 years from WLE. Using data available as of 07-06-2023, Kaplan-Meier (K-M) curves were constructed to estimate the time-to-event distributions for subjects who received RT and for those who did not. The 5-year IBE rates and 95% confidence intervals (CIs) were estimated from K-M curves for all subjects with a DS (analogue of Intention to Treat [ITT] analysis), and for the subset who were compliant with their DS-based RT recommendation (Per Protocol analysis). The analyses were repeated for subgroups based on age at DCIS diagnosis (< 50 vs. ≥ 50). RESULTS. Of 339 women evaluable for the previously reported primary analysis (PMID 30653209), 171 (50.4%) underwent WLE with free surgical margins and had DS available for RT recommendations (ITT population). Of these, 7/82 low DS patients underwent RT, and 5/89 inter/hi DS patients declined RT; thus, the adherence to DS-based RT recommendations was 93%. At a median of 5 years of follow-up from final WLE, the ITT population experienced a total of eight IBE events (4.8%, 95% CI 2.4, 9.4) with 5-year IBE rates that were similar for participants with a low DS and for those with a inter/hi DS: 5.1% (95% CI: 1.9, 12.9) and 4.5% (95% CI 1.7, 11.7), respectively. Stratification by age did not alter these results: among women aged < 50 years (n=33), the IBE rate was 6.7% (95% CI 1.0, 38.7) for low DS and 5.6% (95% CI 0.8, 33.4) for inter/hi DS. Among women aged ≥ 50 years (n=138), the IBE rate was 4.7% (95% CI 1.5, 13.8) for low DS and 4.3% (95% CI 1.4, 12.7) for inter/hi DS. In the per-protocol analysis (N=159 adherent to RT recommendations), IBE rates were also similar for participants who had a low DS and no RT [5.5% (95% CI 2.1, 14.1)] and for those with inter/hi DS who received RT [4.8% (95% CI: 1.8% to 12.3%)]. Again, there was no discernible influence by age as categorized above. CONCLUSION. We report the first prospective data on use of DCIS Score for RT decisions, and 5-year IBE rates. We find that DS-based recommendations are followed by >90% of patients. Although the sample size is limited, the data are reassuring in that the IBE rate is similar between the low DS group treated with WLE alone and the inter/hi DS group treated with WLE and radiation, whereas prior studies have shown a marked difference in IBE rates by DS with excision alone. Therefore, this prospective trial provides strong evidence to support the omission of RT after surgery in DCIS patients with low DS, and its use in patients with intermediate/high DS. Citation Format: Seema Khan, Justin Romanoff, Constantine Gatsonis, Habib Rahbar, Ruth Carlos, Sunil Badve, Jean Wright, Constance Lehman, Worta McCaskill-Stevens, Ralph Corsetti, Derrick Spell, Kenneth Blankstein, Linda Han, Jennifer Sabol, John Bumberry, Ilana Gareen, Bradley Snyder, Lynne Wagner, Kathy Miller, Joseph Sparano, Christopher Comstock. Magnetic Resonance Imaging and a 12-Gene Expression Assay to Optimize Local Therapy for Ductal Carcinoma In Situ: 5-year clinical outcomes of E4112 [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 GS03-01.

Abstract PO4-08-03: Prognostic Effect of Ductal Carcinoma in Situ in Breast Cancer with BRCA1/2 Mutations

Abstract Abstract Background: Although Breast Cancer Susceptibility Gene (BRCA)-associated invasive breast cancer has been extensively studied, there are few reports on ductal carcinoma in situ (DCIS) in patients with BRCA1/2 mutations. This study aims to evaluate the prognostic effect of DCIS in breast cancer patients with pathologic variants of BRCA1/2 genes. Methods: Retrospective analysis was performed on a prospective cohort of 157 patients who were found positive for BRCA1/2 mutations through genetic testing from August 2003 to January 2022 at Seoul National University Bundang Hospital. Survival outcomes were compared between patients who had both invasive ductal carcinoma (IDC) and DCIS components (IDC-DCIS group, n = 121) and patients who had IDC only (IDC group, n = 36). Cox regression analysis was performed for evaluation of predictive factors for recurrence. Results: Among the 157 patients, 65 (41.4%) patients showed BRCA1 mutations, 90 (57.3%) patients had pathological variants of BRCA2, and 2 (1.3%) patients tested positive for both BRCA1/2 mutations. There was no difference in baseline clinical characteristics between the IDC-DCIS and IDC groups. When pathological features were compared, the IDC-DCIS group was more likely to express positivity in both estrogen receptor (IDC 5 (13.9%) vs. IDC-DCIS 74 (61.2%), P < 0.001) and progesterone receptor status (IDC 5 (13.9%) vs. IDC-DCIS 67 (55.4%), P < 0.001). Tumors in the IDC group were associated with a higher histologic grade (P = 0.004). There was no statistically significant difference in 5-year disease-free survival between the two groups (IDC 83.6% vs. IDC-DCIS 89.3%, P = 0.989). In univariate Cox regression analysis, younger age at diagnosis was a significant predictor for recurrence (hazard ratio (HR) 2.236, P = 0.049); salpingo-oophorectomy showed a risk-reducing effect (HR 0.106, P < 0.001). Further multivariate analysis found only the effect of salpingo-oophorectomy to be prognostic (HR 0.112, P < 0.001). Presence of DCIS was not a risk factor for recurrence in patients with BRCA1/2 mutations (HR 1.006, P = 0.989). Conclusion: BRCA1/2-positive breast cancer with DCIS components is more likely to be hormone receptor-positive and of lower grade compared to patients with IDC only. A tailored approach might be necessary in establishing treatment options for breast cancer patients with BRCA1/2 mutations according to the presence of DCIS. Citation Format: Kyung-Hwak Yoon, Eun-Kyu Kim, Hee-Chul Shin. Prognostic Effect of Ductal Carcinoma in Situ in Breast Cancer with BRCA1/2 Mutations [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 PO4-08-03.

Abstract PS01-08: Management of ipsilateral breast tumor recurrence following breast conservation surgery for ductal carcinoma in situ – a data-free zone

Abstract Background: Breast-conserving surgery (BCS) is well established for the management of ductal carcinoma in situ (DCIS). Although a growing body of data support re-conservation therapy (RBCS) for ipsilateral breast tumor recurrence (IBTR) following BCS in invasive cancer, neither randomized trials nor guidelines address management of IBTR following BCS for DCIS. Here we aim to compare the outcomes of mastectomy vs RBCS for a large series of DCIS patients with IBTR. Methods: We identified women treated with BCS for DCIS at MSKCC who developed IBTR as a first event. Between those treated with mastectomy vs RBCS, we compared the clinicopathologic characteristics for the initial and recurrent tumors, the use of adjuvant RT (both upfront (“primary RT”) and post IBTR (“secondary RT”)) and/or tamoxifen, the rate of third events (local, regional, distant), breast cancer specific (BCSS) and overall survival (OS). Results: From our service databases among 3001 women treated with BCS for DCIS (1978-2010), we found 383 who developed an IBTR as a first event and were treated at our institution between 1983-2023, 186 (49%) with RBCS and 197 (51%) with mastectomy. RBCS was more frequent over time and comprised 56% of patients treated between 2014 and 2023. Among those treated with mastectomy, the initial tumors were significantly more likely to have necrosis (74% vs 59%), high grade (47% vs 28%), comedo histology (38% vs 20%), and to have received primary RT at the time of BCS (61% vs 21%). Between those who underwent mastectomy vs RBCS, there were no significant differences in disease-free interval, in the pathologic characteristics of their IBTR, or in the proportion of invasive vs in situ disease. For patients treated with RBCS, 11 (5.9%) received both primary and secondary RT and 77 (41.3%) received neither (Table 1a). For patients treated with a mastectomy only 8.5% had secondary RT (Table 1b). At a median follow-up of 5.1 years post-IBTR, third local events in total were more frequent for RBCS vs mastectomy (16.1% vs 3.0%, 0.001), but there were no differences in BCSS or OS. Among RBCS patients, third local events (breast re-recurrence) were least frequent among those who received primary and secondary RT, and comparable between with who did vs did not receive secondary RT (16% (13/82) vs 16% (117/104), Table 2). Conclusions: Our data show that for women with isolated IBTR following BCS for DCIS and treated by mastectomy vs RBCS, 1) treatment with mastectomy was associated with less favorable initial pathology and more frequent use of primary RT, 2) re-recurrence was more frequent with RBCS, and 3) BCSS and OS were comparable. In an era of increasing surgical de-escalation, our data suggest a wider role for RBCS and – as for patients having RBCS for IBTR following invasive cancer – further study of the relationship between secondary RT and the rate of third breast events. Citation Format: Brian Diskin, Varadan Sevilimedu, Kimberly Van Zee, Monica Morrow, Hiram Cody. Management of ipsilateral breast tumor recurrence following breast conservation surgery for ductal carcinoma in situ – a data-free zone [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 PS01-08.

Nipple-Sparing Mastectomy and Adequate Margins for Patients With Ductal Carcinoma In Situ.

For patients with ductal carcinoma in situ (DCIS) undergoing breast conservation surgery (BCS), guidelines advise a margin width of at least 2mm, with studies demonstrating decreased recurrence risk compared to narrower margins. However, limited data exist establishing if this margin is appropriate in mastectomies, and specifically for nipple-sparing mastectomy (NSM). Consequently, we evaluated the margins of DCIS patients undergoing NSM and resulting oncologic outcomes. A single-institution retrospective review was performed in patients with DCIS or DCIS with microinvasion (DCIS + MI) undergoing NSM from April 2010 to December 2021. Patient and tumor characteristics, margin status, treatment, and outcomes information were collected. The association between margins and local-regional (LRR) and distant recurrence (DR) were examined. 161 patients were included, comprising 284 NSM (164 therapeutic, 120 prophylactic). 153 patients had DCIS and 8 had DCIS + MI. Most patients had hormone sensitive, 123 (76.4%), and nuclear grade 2, 72 (44.7%), disease. In total, 35 (21.7%) patients had positive or <2mm margins. Of these, 21 (60%) involved the anterior margin. At a median follow-up of 45 months (range 0-151), 2.5% (n = 4) had a LRR and .6% (n = 1) had a DR. Of patients with a recurrence, only 2 had positive or <2mm margins, 1 had received endocrine therapy, and none received adjuvant radiation. No specific margin status was found to correlate with recurrence for patients with DCIS or DCIS + MI undergoing NSM, with an altogether low recurrence risk. Overall, this suggests that recommended DCIS margins in BCS doesn't necessarily apply in NSM, where margins of <2mm may be acceptable.

Increase in Hypofractionated Radiation Therapy Among Patients with Invasive Breast Cancer or Ductal Carcinoma In Situ: Who is Left Behind?

We aimed to update the trend of hypofractionated whole-breast irradiation (HF-WBI) use over time in the US and examine factors associated with lack of HF-WBI adoption for patients with early-stage invasive breast cancer (IBC) or ductal carcinoma in situ (DCIS) undergoing a lumpectomy. Among patients who underwent a lumpectomy, we identified 928,034 early-stage IBC patients and 330,964 DCIS patients in the 2004-2020 National Cancer Database. We defined HF-WBI as 2.5-3.33 Gy/fraction to the breast and conventional fractionated whole-breast irradiation as 1.8-2.0 Gy/fraction. We evaluated the trend of HF-WBI utilization using a generalized linear model with the log link and binomial distribution. Factors associated with HF-WBI utilization were assessed using multivariable logistic regression in patients diagnosed between 2018 and 2020. Among IBC patients, HF-WBI use has significantly increased from 0.7% in 2004 to 63.9% in 2020. Similarly, HF-WBI usage among DCIS patients has also increased significantly from 0.4% in 2004 to 56.6% in 2020. Black IBC patients were less likely than White patients to receive HF-WBI (adjusted odds ratio [AOR] 0.81, 95% CI: 0.77-0.85). Community cancer programs were less likely to administer HF-WBI to IBC patients (AOR 0.80, 95% CI: 0.77-0.84) and to those with DCIS (AOR 0.87, 95% CI: 0.79-0.96) than academic/research programs. Younger age, positive nodes, larger tumor size, low volume programs, and facility location were also associated with lack of HF-WBI adoption in both patient cohorts. HF-WBI utilization among post-lumpectomy patients has significantly increased from 2004-2020 and can finally be considered standard of care in the US. We found substantial disparities in adoption within patient and facility subgroups. Reducing disparities in HF-WBI adoption has the potential to further alleviate healthcare costs while improving patients' quality of life.

Deciphering the spatial landscape and plasticity of immunosuppressive fibroblasts in breast cancer

Although heterogeneity of FAP+ Cancer-Associated Fibroblasts (CAF) has been described in breast cancer, their plasticity and spatial distribution remain poorly understood. Here, we analyze trajectory inference, deconvolute spatial transcriptomics at single-cell level and perform functional assays to generate a high-resolution integrated map of breast cancer (BC), with a focus on inflammatory and myofibroblastic (iCAF/myCAF) FAP+ CAF clusters. We identify 10 spatially-organized FAP+ CAF-related cellular niches, called EcoCellTypes, which are differentially localized within tumors. Consistent with their spatial organization, cancer cells drive the transition of detoxification-associated iCAF (Detox-iCAF) towards immunosuppressive extracellular matrix (ECM)-producing myCAF (ECM-myCAF) via a DPP4- and YAP-dependent mechanism. In turn, ECM-myCAF polarize TREM2+ macrophages, regulatory NK and T cells to induce immunosuppressive EcoCellTypes, while Detox-iCAF are associated with FOLR2+ macrophages in an immuno-protective EcoCellType. FAP+ CAF subpopulations accumulate differently according to the invasive BC status and predict invasive recurrence of ductal carcinoma in situ (DCIS), which could help in identifying low-risk DCIS patients eligible for therapeutic de-escalation.

Peripheral blood TCR clonotype diversity as an age-associated marker of breast cancer progression.

Immune escape is a prerequisite for tumor growth. We previously described a decline in intratumor activated cytotoxic T cells and T cell receptor (TCR) clonotype diversity in invasive breast carcinomas compared to ductal carcinoma in situ (DCIS), implying a central role of decreasing T cell responses in tumor progression. To determine potential associations between peripheral immunity and breast tumor progression, here, we assessed the peripheral blood TCR clonotype of 485 breast cancer patients diagnosed with either DCIS or de novo stage IV disease at younger (<45) or older (≥45) age. TCR clonotype diversity was significantly lower in older compared to younger breast cancer patients regardless of tumor stage at diagnosis. In the younger age group, TCR-α clonotype diversity was lower in patients diagnosed with de novo stage IV breast cancer compared to those diagnosed with DCIS. In the older age group, DCIS patients with higher TCR-α clonotype diversity were more likely to have a recurrence compared to those with lower diversity. Whole blood transcriptome profiles were distinct depending on the TCR-α Chao1 diversity score. There were more CD8+ T cells and a more active immune environment in DCIS tumors of young patients with higher peripheral blood TCR-α Chao1 diversity than in those with lower diversity. These results provide insights into the role that host immunity plays in breast cancer development across different age groups.

Treatments and Prognosis of the Breast Ductal Carcinoma In Situ

IntroductionWith progress in treatments, breast ductal carcinoma in situ (DCIS) outcomes have substantially improved. However, as various treatment methods are used in different countries and institutions, consensus on the optimal treatment method is lacking. This study aimed to analyze the prognostic factors and provide a reference for optimizing the clinical treatment of DCIS. Patients and MethodsThis retrospective clinical study collected data from DCIS patients at the Sun Yat-sen University Cancer Center from 2010 to 2017. The Kaplan–Meier method and Cox regression model were used to assess disease-free survival (DFS), overall survival (OS), and local control (LC) rates. ResultsAmong the 483 included patients, 83.6% (404) underwent mastectomies. The median follow-up time was 101 months. The number of patients undergoing breast-conserving surgery (BCS) with radiotherapy has gradually increased. Axillary lymph node dissection was the main surgery performed from 2010 to 2015, and the proportion of sentinel lymph node biopsies (SLNBs) has increased. LC and DFS rates with BCS without radiotherapy were significantly lower than those with mastectomy (P = .002; P < .001). Additionally, the patients who did not undergo axillary surgery had worse LC and OS rates than those who underwent SLNB (P = .028 and P = .038). Endocrine therapy (ET) or its duration had no significant effect on prognosis. ConclusionIn conclusion, BCS without radiotherapy and lack of axillary surgery were independent prognostic factors. We recommend performing BCS with radiotherapy and SLNB more in clinical practice, as well as shortening the ET duration.

Does Endocrine Therapy for DCIS Patients Treated with Breast-Conserving Surgery Followed by Postoperative Radiation Therapy is Needed? A Brazilian Retrospective Cohort Study

International previous clinical trials have demonstrated increased local control. Adjuvant endocrine therapy (ET) is a component of hormone receptor-positive breast ductal carcinoma in situ (DCIS) treatment. Previous trials have shown local control benefits. However, there are still questions regarding the reproducibility of those results in real-life scenarios and for different populations, especially in patients who received breast-conserving surgery followed by postoperative radiation therapy. Therefore, we retrospectively evaluated the impact of adjuvant ET for CDIS from a large State database in Brazil. We retrospectively evaluated the Fundação Oncocentro de São Paulo (FOSP) database, which collects information on hospitals and oncology departments in the State of São Paulo, Brazil. The endpoints were local control (LC), disease-specific survival (DSS), and overall survival (OS). Moreover, we investigated the influence of medical practice (public health care system, insurance, private) and educational level (illiterate and incomplete middle school were grouped as low; complete middle school, high school, and undergraduate were grouped as medium/high). Data from 2,192 patients who underwent breast-conserving surgery and postoperative radiotherapy and were treated between 2000 and 2020 were analyzed. The median follow-up time was 48.99 months (IQR 29.93 - 88.67). In the cohort, 53.33% (n = 1169) of patients received adjuvant ET, and 46.67% did not (n = 1023). Overall, patients not receiving adjuvant ET tend to be older (p = 0.021) and have a lower educational level (p < 0.001). Median OS and DSS were not reached. The 10-year OS and DSS for patients receiving adjuvant ET versus those not receiving it was 89.36% vs. 91.47% and 97.54% vs. 98.48%, respectively. The HR for OS for adjuvant ET vs. no ET was 0.96 (95% CI 0.63 - 1.4; p = 0.83). The HR for DSS for adjuvant ET vs. no ET was 0.79 (95% CI 0.29 - 2.12; p = 0.63). The only variable associated with survival was educational level. The 10-year OS was significantly higher for patients with medium/high educational levels (93.25% vs. 87.31%). The HR for death for medium/high versus low educational level was 0.51 (95% CI 0.32 - 0.83; p = 0.007). Recurrence rates were low in the cohort. Only 1.5% of patients had local recurrence, and 0.2% had a regional recurrence. There was no significant difference between recurrence rates for adjuvant ET (p = 0.19 and p = 0.78, respectively). The benefits of adjuvant ET in DCIS patients found in international clinical trials could not be demonstrated in a Brazilian cohort. Educational level significantly impacted survival and ET usage, reflecting the influence of socioeconomic factors. Identifying these more vulnerable populations can allow for more precise interventions.

Standardizing Breast Adjuvant Radiation Therapy Practices in a Diverse Health System through Development of a Delphi Consensus Supported Clinical Algorithm

Adjuvant radiation therapy (RT) for early breast cancer is a highly effective treatment option. However, the multitude of available techniques backed by strong clinical evidence can result in a lack of consistency in treatment approaches, even within a single healthcare organization. This presents challenges for both providers and patients in making informed decisions. To address this issue, our radiation department, which serves a large and diverse health system, developed a clinical algorithm for adjuvant RT for breast cancer. This algorithm was created to enhance the quality and standardization of care delivered across our network. A modified Delphi technique was used. A panel of eight experienced breast radiation oncologists from our institution was assembled. The panel first identified the common clinical scenarios encountered in treating patients with adjuvant breast RT, and then made recommendations for the primary and alternative approaches for each scenario. NCCN guidelines, ASTRO executive summaries, and published national and international randomized trials were used for reference. In case of disagreements, the final recommendation was reached through a majority vote. The draft algorithm was also shared with medical oncologists, surgeons, and patient advocates to gather their input prior to final approval by the expert panel. Consensus was reached for three broad clinical scenarios for patients who have undergone lumpectomy or mastectomy: Ductal Carcinoma in Situ (DCIS), Invasive Cancer Node Negative (ICN0), and Invasive Cancer Node Positive (ICN+). The panel agreed subdivision of the scenarios into three risk groups (low, intermediate, and high) and three age groups, based on guidelines and consensus statements. For DCIS patients, size, grade, margin status, hormone receptor status, and tumor focality were used for further stratification. For ICN0 patients, HER2 receptor status and lymphovascular space invasion were also included. For ICN+ patients, nodal status (negative versus 1-3 positive nodes versus more than 3 positive nodes) was used for stratification. Additionally, DCIS and ICN0 patients were further divided into age groups. The panel reached consensus recommendations for RT, including whole breast RT, partial breast RT, chest wall RT, regional nodal irradiation, or omission of RT for each sub-group. Clinical trial enrollment was also recommended where appropriate. A breast cancer adjuvant RT algorithm was developed with the aim of standardizing care for patients with breast cancer. Implementation is expected to standardize treatment recommendations in our health system and to streamline the shared decision-making process with patients.

Locoregional Control Benefit of a Tumor Bed Boost for Ductal Carcinoma In Situ (DCIS)

Radiotherapy (RT) following breast conserving surgery (BCS) for ductal carcinoma in situ (DCIS) reduces invasive and in situ recurrences. Whereas landmark studies suggest that a tumor bed boost improves local control for invasive breast cancer, the benefit in DCIS remains less certain. We evaluated outcomes of DCIS patients treated with or without a boost and hypothesized that a tumor bed boost would improve locoregional control rates. The study cohort comprised patients with DCIS who underwent BCS at our institution from 2004-2018. Clinicopathologic features, treatment parameters and outcomes were ascertained from medical records. Patient and tumor characteristics were evaluated relative to outcomes using univariable and multivariable Cox models. Recurrence-free survival (RFS) estimates were generated using the Kaplan Meier method. We identified 1675 patients who underwent BCS for DCIS (median age 56 [interquartile range (IQR) 49, 64]). Boost RT was employed in 68% of cases (n = 1146) and endocrine therapy in 32% (n = 536). At a median follow-up of 4.2 years (IQR 1.4, 7.0), we observed 61 locoregional recurrence events (56 local, 5 regional) and 21 deaths. Univariable logistic regression demonstrated that boost RT was more common among younger patients (p<0.001) with positive/close margins (p<0.001), and with larger tumors (p<0.001) of higher grade (p = 0.025). The 10-year RFS rate was 88.8% among those receiving a boost and 84.3% among those without a boost (p = 0.3), and neither univariable nor multivariable analyses revealed an association between boost RT and locoregional recurrence. Among patients with DCIS who underwent BCS, use of a tumor bed boost was not associated with locoregional recurrence or RFS. Despite a preponderance of adverse features among the boost cohort, outcomes were similar to those not receiving a boost, suggesting that a boost may mitigate risk of recurrence among patients with high-risk features. Ongoing studies will elucidate the extent to which a tumor bed boost influences disease control rates.

Clinical presentations and outcomes of young women aged

Ductal carcinoma in situ (DCIS) in young women is rare and not well studied. Since they do not qualify for mammographic screening, they are more likely to present with symptoms. Young women have also been associated with poorer outcomes, but it is unknown whether presentation mode affects outcome. We aimed to compare characteristics of DCIS patients <40 years of age presenting with symptoms versus those without, and determine whether presentation mode affects recurrence. Pure DCIS patients aged <40 years were retrospectively analyzed. Clinical presentation, pathology and recurrence data were collected. Statistical analysis was performed to investigate the correlation of presentation mode with outcomes. 40 patients with 41 cases were included. The mean age at diagnosis was 32.3 years (range 17-39). 73.2% and 26.8% presented with symptoms or abnormal imaging respectively. Of the cases who presented with symptoms, 86.7%, 10.0% and 3.3% had palpable lump, nipple discharge or breast pain, respectively. The average tumor size was 22.0 mm (range 2.0-86.9) and 12.2 mm (range 3-25) for patients who presented with symptoms and non-symptomatic group, respectively. Cases presenting with symptoms were statistically associated with higher grade (p =0.0090). On median follow-up of 85 months, there were 3 (7.3%) recurrences, which were not statistically associated with presentation mode. Young women with DCIS tend to present with symptoms, with breast lump as the commonest symptom. Symptomatic patients tend to be associated with grade III tumours, compared to non-symptomatic patients. On long-term follow-up, mode of presentation was not statistically associated with recurrence.

Preoperative factors associated with underestimation of invasive breast cancer in stereotactic vacuum-assisted biopsy-diagnosed DCIS patients

Objective: To determine preoperative factors associated with underestimation of invasive breast cancer, where stereotactic vacuum-assisted biopsy (VAB) diagnosed as ductal carcinoma in situ (DCIS). Materials and Methods: Data from 95 patients diagnosed with DCIS by stereotactic VAB, including their clinical, radiological, and pathological findings between November 2010 and May 2021, were analyzed retrospectively. The clinical, radiological, and pathological features were analyzed. Results: The underestimation rate was 30.5 %. Three preoperative features were significantly associated with the underestimation of invasive breast cancer in multivariable analysis, including palpability (OR, 11.51; 95% CI: 1.817-72.897; P = 0.009), BI-RADS category (OR, 3.705; 95% CI: 1.214-11.303; P = 0.021), and visibility of a mammographically detected lesion at ultrasonography (OR, 7.115; 95% CI: 1.977-25.611; P = 0.003). The calcification morphology was statistically significant in an univariable analysis but not in a multivariable analysis. Conclusion: Preoperative variables significantly associated with underdiagnosis of invasive breast cancer, including palpability, BI-RADS category, and visibility of mammographically detected lesions at ultrasonography, could aid in assessing the risk of developing invasive breast cancer and conducting treatment selection.

Estrogen Receptor-negative Ductal Carcinoma In Situ (DCIS) of the Breast - an Institutional Review of Outcomes.

Estrogen receptor (ER)-negative [ER(-)] invasive breast cancers (IBCs) are known to be more aggressive than their ER(+) counterparts. This is less well defined for ductal carcinoma in situ (DCIS). This study investigated the outcomes following the treatment of ER(-) DCIS. A total of 103 ER(-) DCIS patients diagnosed between 2004-2018 were retrospectively analyzed. Median follow-up was 63.9 months. Statistical analysis included descriptive statistics, non-parametric tests, T-test, logistic regression. The outcomes were compared to a group of 102 ER(+) DCIS patients from our institution. Any breast event (BE) occurred in 10 (9.7%) patients at a median of 3.2 (1.7-7.2) years. The incidence of ipsilateral breast events (IBEs) was 5.8% (6/103). All IBE cases were ER(-) DCIS. All (n=4) contralateral breast events (CBEs) were ER(+) including 3 IBCs. Cumulative incidence of any BEs at 1, 2, and 5 years was 0%, 1.1%, and 9.1%, respectively. Among patients with ER(-) DCIS who developed BE, breast conserving surgery (BCS) had been performed for the initial DCIS in 90% of cases. In those without any BE, the BCS rate (vs. mastectomy) was 58.1% (p=0.08). Adjuvant radiotherapy after BCS was used less often among patients with vs. without subsequent BE (55.5% vs. 77.4%) (p=0.22). Predictors for BE occurrence were not identified. The incidence of any BE among patients with ER(+) DCIS was 6.9% and was not significantly different compared to ER(-) DCIS group (p=0.46). ER(-) DCIS outcomes were similar to our institutional ER-positive DCIS group and the previously reported ones for predominantly ER-positive DCIS cohorts.

Real-World Evidence on the Use of Endocrine Therapy for Ductal Carcinoma In Situ in Patients Treated With Breast-Conserving Surgery Followed by Postoperative Radiation Therapy: A Brazilian Retrospective Cohort Study

Introduction/BackgroundThis study aims to evaluate the reproducibility of findings from randomized controlled trials regarding adjuvant hormone therapy (HT) for breast ductal carcinoma in situ (DCIS) in a real-life scenario. Materials/MethodsThis retrospective cohort study used Fundação Oncocentro de São Paulo database. It included DCIS patients DCIS who received breast-conserving surgery and postoperative radiation therapy. The endpoints were local control (LC), breast cancer-specific survival (BCSS), and overall survival (OS). ResultsWe analyzed 2192 patients treated between 2000 and 2020. The median FU was 48.99 months. Most patients (53.33%; n = 1169) received adjuvant HT. Patients not receiving adjuvant HT tend to be older (P = .021) and have a lower educational level (P < .001). At the end of FU, 1.5% of patients had local recurrence, and there was no significant difference between groups (P = .19). The 10-year OS and BCSS were 89.4% and 97.5% for adjuvant HT versus 91.5% and 98.5% for no adjuvant HT, respectively, and there were no significant differences between groups. The 10-year OS was 93.25% for medium/high education level versus 87.31% for low (HR for death 0.51; 95% CI, 0.32-0.83; P = .007). ConclusionsThe benefits of adjuvant HT for DCIS were not reproduced in a Brazilian cohort. Education significantly impacted survival and HT usage, reflecting the influence of socioeconomic factors. These findings can allow for more precise interventions.

Ipsilateral tumor recurrence risk in women with ductal carcinoma in situ: application of the Van Nuys Prognostic Index and the Memorial Sloan Kettering Cancer Center nomogram.

To apply the Van Nuys Prognostic Index (VNPI) and the Memorial Sloan Kettering Cancer Center (MSKCC) ductal carcinoma in situ (DCIS) nomogram to DCIS patients with known long-term outcomes. A retrospective review was performed of consecutive patients diagnosed with DCIS from 2007 to 2014. Included patients underwent breast-conserving surgery (BCS) and were followed with imaging for at least five years. For each patient, the VNPI and MSKCC nomogram risk estimates were determined. In addition, variables used in both models were compared between women with and without recurrences using the Wilcoxon signed-rank test and the Pearson's chi-squared test. Over the eight-year period, 456 women (average age 57 years, range 30-87) underwent BCS for DCIS. Thirty-one (6.8%) experienced an ipsilateral recurrence. The average VNPI scores were 7 (range 5-9) and 7 (range 4-10) for women with and without a recurrence (p = 0.14), respectively, with 4-6, 7-9, and 10-12 being the low, moderate, and high-risk groups, respectively. Per the MSKCC nomogram, the average five-year recurrence risks were 5% (range 1-12%) and 4% (range 1-38%) for women with and without a recurrence (p = 0.09), respectively. The recurrence risk-related variables were younger patient age, need for one or more re-excision surgeries, and use of endocrine therapy for 0 to less than five years after surgery. Ipsilateral tumor recurrence risk estimates based on the VNPI and MSKCC nomogram are similar between women with DCIS who did and did not have a recurrence, suggesting that more robust prognostic models are needed.

Germline Genetic Testing Among Women ≤ 45Years of Age with Ductal Carcinoma In Situ Versus Invasive Breast Cancer in a Large Integrated Health Care System.

We compared the results of hereditary cancer multigene panel testing among patients ≤ 45years of age diagnosed with ductal carcinoma in situ (DCIS) versus invasive breast cancer (IBC) in a large integrated health care system. A retrospective cohort study of hereditary cancer gene testing among women ≤ 45years of age diagnosed with DCIS or IBC at Kaiser Permanente Northern California between September 2019 and August 2020 was performed. During the study period, institutional guidelines recommended the above population be referred to genetic counselors for pretesting counseling and testing. A total of 61 DCIS and 485 IBC patients were identified. Genetic counselors met with 95% of both groups, and 86.4% of DCIS patients and 93.9% of IBC patients (p = 0.0339) underwent gene testing. Testing differed by race/ethnicity (p = 0.0372). Among those tested, 11.76% (n = 6) of DCIS patients and 16.71% (n = 72) of IBC patients had a pathogenic variant (PV) or likely pathogenic variant (LPV) based on the 36-gene panel (p = 0.3650). Similar trends were seen in 13 breast cancer (BC)-related genes (p = 0.0553). Family history of cancer was significantly associated with both BC-related and non-BC-related PVs in IBC, but not DCIS. In our study, 95% of patients were seen by a genetic counselor when age was used as an eligibility criterion for referral. While larger studies are needed to further compare the prevalence of PVs/LPVs among DCIS and IBC patients, our data suggest that even in younger patients, the prevalence of PVs/LPVs in BC-related genes is lower in DCIS patients.