DCIS Topic-Driven Round Table: Decision-Making and Treatment Choices

Editor's Notes

• #10: Main points: Advances in diagnosis and screening have led to an increase in the number of patients with DCIS. In 2005, 500,000 women were estimated to be living in the US with a diagnosis of DCIS; this number is expected to reach 1 million in 2020. However, treatment decision making has not evolved to keep pace with the advances in detection of these tumors. The traditional measures for assessing risk of recurrence for DCIS are similar to the clinical and pathologic measures used to assess risk of recurrence in invasive breast cancer: age, residual tumor/margin width, grade, histology, size and menopausal status. None of these characteristics, however, provide a quantitative assessment of recurrence risk. Alvarado et al. J Surg Oncol. 2015. Allegra et al. J Natl Cancer Inst. 2010. Leonard et al. SABCS 2016.
• #11: Main Points: Goal of screening mammography is to detect small malignant tumors before they grow large enough to cause symptoms Widespread implementation of screening mammography occurred in the 1980s Incidence of DCIS increased sharply as a result of widespread screening while incidence of invasive breast cancer remain constant Virnig et al. AHRQ 2009.
• #12: This presentation is focused upon harnessing the power of genomics for DCIS management. Foremost in the clinician’s mind is the question of how to make a treatment decision for the patient. These decisions vary according to patient preference, and goals of treatment must be aligned with the patient’s own goals. The decision around recommending XRT is dependent on an assessment of LR risk with an assumption that around half of those recurrences will be invasive disease. While reduction of LR is important, particularly invasive LR, other goals of therapy are taken into consideration such as the cosmetic outcomes and the side effects from XRT. Currently LR risk is estimated based on clinicopathologic factors and provides an average risk derived from population studies. No studies have been able to identify a patient group that did not derive benefit (i.e. risk reduction) with XRT.
• #13: This presentation is focused upon harnessing the power of genomics for DCIS management. Foremost in the clinician’s mind is the question of how to make a treatment decision for the patient. These decisions vary according to patient preference, and goals of treatment must be aligned with the patient’s own goals. The decision around recommending XRT is dependent on an assessment of LR risk with an assumption that around half of those recurrences will be invasive disease. While reduction of LR is important, particularly invasive LR, other goals of therapy are taken into consideration such as the cosmetic outcomes and the side effects from XRT. Currently LR risk is estimated based on clinicopathologic factors and provides an average risk derived from population studies. No studies have been able to identify a patient group that did not derive benefit (i.e. risk reduction) with XRT.
• #14: This presentation is focused upon harnessing the power of genomics for DCIS management. Foremost in the clinician’s mind is the question of how to make a treatment decision for the patient. These decisions vary according to patient preference, and goals of treatment must be aligned with the patient’s own goals. The decision around recommending XRT is dependent on an assessment of LR risk with an assumption that around half of those recurrences will be invasive disease. While reduction of LR is important, particularly invasive LR, other goals of therapy are taken into consideration such as the cosmetic outcomes and the side effects from XRT. Currently LR risk is estimated based on clinicopathologic factors and provides an average risk derived from population studies. No studies have been able to identify a patient group that did not derive benefit (i.e. risk reduction) with XRT.
• #16: This presentation is focused upon harnessing the power of genomics for DCIS management. Foremost in the clinician’s mind is the question of how to make a treatment decision for the patient. These decisions vary according to patient preference, and goals of treatment must be aligned with the patient’s own goals. The decision around recommending XRT is dependent on an assessment of LR risk with an assumption that around half of those recurrences will be invasive disease. While reduction of LR is important, particularly invasive LR, other goals of therapy are taken into consideration such as the cosmetic outcomes and the side effects from XRT. Currently LR risk is estimated based on clinicopathologic factors and provides an average risk derived from population studies. No studies have been able to identify a patient group that did not derive benefit (i.e. risk reduction) with XRT.
• #17: Main Points: A clinician's treatment decision varies according to a patient’s perceived risk of recurrence in addition to patient preference Multiple factors influence treatment decisions Estimated risk of local recurrence local recurrence based on clinical and pathologic features Estimated risk of invasive LR (approximately 50% of recurrences) Balancing toxicity of therapy for a non-life-threatening disease Patient preference Although DCIS is not a lethal disease, the same treatments (or combination of treatments) are offered as patients with invasive breast cancer All standard treatments are given to reduce risk of local recurrence, however, side-effects with each treatment option must be considered on an individual basis Additional considerations regarding standard treatment options for DCIS: If a patient receives BCS + RT for DCIS and has an invasive recurrence, mastectomy is the only remaining surgical option. However, patients with an invasive recurrence that received BCS alone for DCIS may have the option of receiving BCS to remove the invasive recurrence Radiation therapy reduces LR by 50% but has not been shown to impact overall or disease-free survival Additional considerations for patients receiving radiation therapy include cost, distance patient needs to travel for RT Compliance is a large barrier with regards to hormonal therapy treatment for ER+ DCIS patients Allegra et al. J Natl Cancer Inst. 2010.
• #18: Main Points based on NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Version 2.2019: The NCCN Guidelines® for DCIS treatment include breast conserving surgery with or without radiation or mastectomy/reconstruction The treatment algorithm is accompanied by the following footnote: “…If the patient and physician view the individual’s risk as ‘low,’ some patients may be treated by excision alone.” Physician and patient perceptions of low risk will vary greatly, therefore the need to accurately asses a patient’s individual risk of local recurrence is critical to how the patient is clinically managed Use of the clinical/pathologic features alone have not been shown to accurately identify a group of patients whose risk of local recurrence is low enough to safely omit adjuvant radiation from the patient’s treatment plan Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.2.2019. © 2019. National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available.
• #21: Main Points: The Oncotype Breast DCIS Score® test is the only genomic assay that can assess an individual DCIS patient’s local recurrence risk The activity of 7 genes in critical molecular pathways is quantitatively measured to determine the DCIS Score® result that reflects the underlying biology of the tumor 7 cancer related genes (proliferation group, progesterone receptor (PR) and GSTM1) are included in the assay and are purely prognostic. The combined expression of these genes within a proprietary algorithm generates a DCIS Score result that provides an individual’s risk of any ipsilateral local recurrence and specifically risk of an invasive local recurrence ER gene is not included in the DCIS Score result as ER expression is predictive of endocrine therapy benefit and is not prognostic Solin et al. J Natl Cancer Inst. 2013.
• #23: Main Point: Only the Oncotype DX® Breast DCIS Score™ report combines clinicopathologic features and tumor biology for an individualized determination of 10-year risk of local or invasive local recurrence Solin et al. J Natl. Cancer Inst. 2013. Rakovitch et al. Breast Cancer Res Treat. 2015. Rakovitch et al. ASCO 2017.
• #26: Main Points: The first validation study was carried out in a prospective cohort study of patients Based on clinicopathological covariates (tumor grade and size) these patients were believed to have had a low-risk of local recurrence Hughes et al. J Clin Oncol. 2009.
• #27: Main Points: In the high-risk group (red), the estimated 10-year percentage of patients free of any LR was 74%, with the low Breast DCIS Score™ risk group (green) having an estimated 89% of patients free of LR. The log rank P-value of 0.006 means that there was a significant trend in LR risk across the three Breast DCIS Score risk groups For invasive local recurrence, the high Breast DCIS Score risk group (red) had an estimated 81% of patients LR-free at 10 years, while in the low Breast DCIS Score risk group (green), 96% of patients were estimated to be LR-free at 10 years. The log rank P-value of 0.003 means that there was a significant trend in invasive LR risk across the three Breast DCIS Score risk groups While the E5194 population was generally believed to be at low-risk, it is important to note that 70% of the patients were in the low Breast DCIS Score risk group and 30% were in the intermediate or high-risk groups Solin et al. J Natl. Cancer Inst. 2013. Genomic Health, Data on File.
• #28: Main Point: The estimation of 10-year risk of local recurrence risk evaluated as a continuous function shows that increasing Breast DCIS Score™ result is associated with increasing risk of local recurrence (any recurrence or invasive recurrence) in the E5194 study using a Cox proportional hazards model Solin et al. J Natl. Cancer Inst. 2013.
• #29: Main Points: The risk curves generated across these two different studies were highly similar We see a similar distribution in risk group across both studies as well Solin et al. J Natl Cancer Inst. 2013. Rakovitch et al. Breast Cancer Res Treat. 2015.
• #31: Main Points: Clinical and pathologic features such as tumor size, patient age, and tumor grade have been shown to be independently prognostic, proving an estimated risk of local recurrence for the average patient with similar features The DCIS Score® result provides insight into the patient’s underlying tumor biology, providing an individualized risk estimate beyond just clinical and pathologic features alone The DCIS Score result can identify patients whose risk of local recurrence is higher or lower than the relevant clinical and pathologic factors would suggest, allowing physicians to tailor treatment discussions and recommendations based on an individualized risk estimate Combining clinical and pathologic features with the DCIS Score result may improve the precision with which the test can provide an individual’s risk of local recurrence (DCIS or invasive cancer) after breast-conserving surgery alone
• #32: Main Points: A patient-specific meta-analysis including data from patients from both E5194 and the Ontario cohort study was performed to determine how the DCIS Score® result could be combined with clinical and pathologic factors to provide the most precise risk assessment for each individual patient Pre-specified prognostic factors studied were: DCIS Score result Age at diagnosis (<50 years, ≥50 years) Tumor size (≤1 cm, >1-2.5 cm, >2.5 cm) An additional covariate was analyzed: year of diagnosis (before year 2000, year 2000 or later to more accurately reflect modern clinical practice) The meta-analysis integrating DCIS Score result, age, and tumor size: Risk estimates were produced for individual patients (from each cohort) based on patient covariate values Risk information was combined across cohorts using patient-specific meta-analysis Precision-weighted estimates of 10-year risk of local recurrence and invasive local recurrence were calculated Did not include patients with positive margins or multifocal disease Tumor grade was not found to be a significant prognostic factor in this patient-specific meta-analysis, nor was it significant in the independent validation studies Rakovitch et al. J Natl Cancer Inst. 2017.
• #33: Main Points: The DCIS meta-analysis, presented at ASCO 2017, uses the ECOG E5194 and Ontario cohorts and identified year of surgery, patient age at time of diagnosis, and tumor size as consistently informative prognostic clinicopathologic factors By integrating the Breast DCIS Score™ with year of surgery, patient age at time of diagnosis, and tumor size a more refined risk estimate can be generated for patients It should be noted, the Breast DCIS Score remains the same, however, the associated percent risk of recurrence will change after integrating the patient’s age at time of diagnosis, tumor size, and surgery after the year 2000 Approximately 53% of patients in the Ontario cohort were ≥50 y.o. and had ≤1 cm tumors Solin et al. J Natl. Cancer Inst. 2013. Rakovitch et al. Breast Cancer Res Treat. 2015. Rakovitch et al. ASCO 2017.
• #36: Main Points: The first page of the DCIS report clearly displays the patient’s Breast DCIS Score™ result as well as a written description explaining the assay result was combined with the patient’s age and tumor size to determine a patient’s 10-year percent risk of recurrence estimate The rest of the report clearly identifies the patient’s age category [≥ 50 or <50] and tumor size category (> 1 cm or ≤ 1 cm), summarizes the meta-analysis study, and provides risk estimates for any local recurrence (invasive or DCIS) and invasive only local recurrence The second page of the DCIS report provides quantitative single gene results for ER and PR
• #37: Main Points: The first page of the DCIS report clearly displays the patient’s Breast DCIS Score™ result as well as a written description explaining the assay result was combined with the patient’s age and tumor size to determine a patient’s 10-year percent risk of recurrence estimate The rest of the report clearly identifies the patient’s age category [≥ 50 or <50] and tumor size category (> 1 cm or ≤ 1 cm), summarizes the meta-analysis study, and provides risk estimates for any local recurrence (invasive or DCIS) and invasive only local recurrence The second page of the DCIS report provides quantitative single gene results for ER and PR
• #39: This was a prospectively enrolled observational study of newly diagnosed patients with histologically proven pure DCIS; 115 patients were evaluated. 122 patients were enrolled at 10 centers throughout the US from September 2012 to February 2014 115 patients were evaluable for the primary analysis The 122 patients were enrolled by 5 radiation oncologists (48 pts; 41.7%) and 5 surgeons (67 pts; 58.3%) Sites: RMCC, Denver CO- 48 pts; SCCA, Little Rock, AR- 28 pts; CH, Cincinnati, OH- 15 pts; UCSF, San Francisco, CA- 9 pts; SJMC, Baltimore, MD- 9 pts; SEH, Cincinnati, OH- 6 pts Physicians filled out standardized questionnaires prior to and after the DCIS Score results were known; patient and tumor characteristics were extracted from the medical record Inclusion Criteria: ≥18 years old, female Histologically proven DCIS Eligible for breast conserving therapy Surgical excision pathology report available Oncotype DX® Breast Cancer Assay for DCIS ordered but result not yet available Exclusion Criteria: LCIS without DCIS Invasive carcinoma Mastectomy planned
• #40: Prior to receiving the DCIS Score result, physicians recommended XRT for 73% of patients. After receiving the assay results, XRT was recommended only for 59.1% of patients. This resulted in a net change of 31.3% in treatment recommendations.
• #41: The change in XRT recommendation by DCIS Score result had the greatest impact in the low risk group; overall, treatment recommendations changed 31.3% of the time.
• #43: The DCIS Score™ result facilitates treatment decisions by increasing clarity, comfort and confidence in your patient’s treatment plan.
• #44: Main Point: Only the Oncotype DX Breast DCIS Score® report combines clinicopathologic features and tumor biology for an individualized determination of 10-year risk of local or invasive local recurrence Solin et al. J Natl. Cancer Inst. 2013. Rakovitch et al. Breast Cancer Res Treat. 2015. Rakovitch et al. J Natl Cancer Inst. 2017.
• #49: Main Points: The second validation study was carried out in a real-world patient cohort that was not restricted as to margins, tumor grade, or size Therefore, this is a more stringent test of the performance of the assay Rakovitch et al. Breast Cancer Res Treat. 2015.
• #50: Main Points: In the analysis, patients had breast-conserving surgery alone with clear margins For the invasive local recurrence alone graph, the intermediate group demonstrates a higher risk of recurrence than the high-risk group. This unexpected result is likely due to the relatively small numbers within each group Rakovitch et al. Breast Cancer Res Treat. 2015.