Dataset Information

Association of Residual Ductal Carcinoma In Situ With Breast Cancer Recurrence in the Neoadjuvant I-SPY2 Trial.

ABSTRACT:

Importance

Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer strongly correlates with overall survival and has become the standard end point in neoadjuvant trials. However, there is controversy regarding whether the definition of pCR should exclude or permit the presence of residual ductal carcinoma in situ (DCIS).

Objective

To examine the association of residual DCIS in surgical specimens after neoadjuvant chemotherapy for breast cancer with survival end points to inform standards for the assessment of pathologic complete response.

Design, setting, and participants

The study team analyzed the association of residual DCIS after NAC with 3-year event-free survival (EFS), distant recurrence-free survival (DRFS), and local-regional recurrence (LRR) in the I-SPY2 trial, an adaptive neoadjuvant platform trial for patients with breast cancer at high risk of recurrence. This is a retrospective analysis of clinical specimens and data from the ongoing I-SPY2 adaptive platform trial of novel therapeutics on a background of standard of care for early breast cancer. I-SPY2 participants are adult women diagnosed with stage II/III breast cancer at high risk of recurrence.

Interventions

Participants were randomized to receive taxane and anthracycline-based neoadjuvant therapy with or without 1 of 10 investigational agents, followed by definitive surgery.

Main outcomes and measures

The presence of DCIS and EFS, DRFS, and LRR.

Results

The study team identified 933 I-SPY2 participants (aged 24 to 77 years) with complete pathology and follow-up data. Median follow-up time was 3.9 years; 337 participants (36%) had no residual invasive disease (residual cancer burden 0, or pCR). Of the 337 participants with pCR, 70 (21%) had residual DCIS, which varied significantly by tumor-receptor subtype; residual DCIS was present in 8.5% of triple negative tumors, 15.6% of hormone-receptor positive tumors, and 36.6% of ERBB2-positive tumors. Among those participants with pCR, there was no significant difference in EFS, DRFS, or LRR based on presence or absence of residual DCIS.

Conclusions and relevance

The analysis supports the definition of pCR as the absence of invasive disease after NAC regardless of the presence or absence of DCIS.

Trial registration

ClinicalTrials.gov Identifier NCT01042379.

SUBMITTER: Osdoit M

PROVIDER: S-EPMC9453630 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of Residual Ductal Carcinoma In Situ With Breast Cancer Recurrence in the Neoadjuvant I-SPY2 Trial.

Osdoit Marie M Yau Christina C Symmans W Fraser WF Boughey Judy C JC Ewing Cheryl A CA Balassanian Ron R Chen Yunn-Yi YY Krings Gregor G Wallace Anne M AM Zare Somaye S Fadare Oluwole O Lancaster Rachael R Wei Shi S Godellas Constantine V CV Tang Ping P Tuttle Todd M TM Klein Molly M Sahoo Sunati S Hieken Tina J TJ Carter Jodi M JM Chen Beiyun B Ahrendt Gretchen G Tchou Julia J Feldman Michael M Tousimis Eleni E Zeck Jay J Jaskowiak Nora N Sattar Husain H Naik Arpana M AM Lee Marie Catherine MC Rosa Marilin M Khazai Laila L Rendi Mara H MH Lang Julie E JE Lu Janice J Tawfik Ossama O Asare Smita M SM Esserman Laura J LJ Mukhtar Rita A RA

JAMA surgery 20221101 11

<h4>Importance</h4>Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer strongly correlates with overall survival and has become the standard end point in neoadjuvant trials. However, there is controversy regarding whether the definition of pCR should exclude or permit the presence of residual ductal carcinoma in situ (DCIS).<h4>Objective</h4>To examine the association of residual DCIS in surgical specimens after neoadjuvant chemotherapy for breast cancer with ...[more]

PMID: 36069821

Similar Datasets

Project description:BackgroundThe accurate evaluation of favorable response to neoadjuvant chemotherapy (NCT) is critical to determine the extent of surgery. We investigated independent clinicopathological and radiological predictors to discriminate no residual carcinoma (ypT0) from residual ductal carcinoma in situ (ypTis) in breast cancer patients who received NCT.Patients and methodsParameters of 117 patients attaining pathological complete response (CR) in the breast after NCT between January 2010 and December 2013 were retrospectively evaluated by univariate and multivariate analyses. All patients underwent mammography, ultrasound, and magnetic resonance imaging (MRI) before and after NCT.ResultsThere were 67 (57.3%) patients with ypT0. These patients were associated with hormone receptor-negative status, human epidermal growth factor receptor-2 (HER2)-negative tumors, and a higher likelihood of breast-conservation surgery. Baseline mammographic and MRI presentation of the main lesion, absence of associated microcalcifications, shape, posterior features, and absence of calcifications on ultrasound were significantly associated with ypT0. CR in mammography, ultrasound, or MRI after NCT was also related to ypT0. By multivariate analysis, independent predictors of ypT0 were the triple-negative subtype [Odds ratio (OR), 4.23; 95% confidence interval (CI), 1.11-16.09] and CR in MRI after NCT (OR, 5.23; 95% CI, 1.53-17.85). Stratified analysis by breast cancer subtype demonstrated that MRI well predicted ypT0 in all subtypes except the HER2-positive subtype. In particular, of 40 triple-negative subtypes, 22 showed CR in MRI and 21 (95.5%) were ypT0 after NCT.ConclusionAmong imaging modalities, breast MRI can potentially distinguish between ypT0 and ypTis after NCT, especially in patients with triple-negative breast cancer. This information can help clinicians evaluate tumor response to NCT and plan surgery for breast cancer patients of all subtypes except for those with HER2-enriched tumors after NCT.

Project description:ObjectiveTo develop a nomogram that integrates clinical-pathologic and imaging variables to predict ipsilateral breast tumor recurrence (IBTR) in women with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS).Materials and methodsThis retrospective study included consecutive women with DCIS who underwent BCS at two hospitals. Patients who underwent BCS between 2003 and 2016 in one hospital and between 2005 and 2013 in another were classified into development and validation cohorts, respectively. Twelve clinical-pathologic variables (age, family history, initial presentation, nuclear grade, necrosis, margin width, number of excisions, DCIS size, estrogen receptor, progesterone receptor, radiation therapy, and endocrine therapy) and six mammography and ultrasound variables (breast density, detection modality, mammography and ultrasound patterns, morphology and distribution of calcifications) were analyzed. A nomogram for predicting 10-year IBTR probabilities was constructed using the variables associated with IBTR identified from the Cox proportional hazard regression analysis in the development cohort. The performance of the developed nomogram was evaluated in the external validation cohort using a calibration plot and 10-year area under the receiver operating characteristic curve (AUROC) and compared with the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram.ResultsThe development cohort included 702 women (median age [interquartile range], 50 [44-56] years), of whom 30 (4%) women experienced IBTR. The validation cohort included 182 women (48 [43-54] years), 18 (10%) of whom developed IBTR. A nomogram was constructed using three clinical-pathologic variables (age, margin, and use of adjuvant radiation therapy) and two mammographic variables (breast density and calcification morphology). The nomogram was appropriately calibrated and demonstrated a comparable 10-year AUROC to the MSKCC nomogram (0.73 vs. 0.66, P = 0.534) in the validation cohort.ConclusionOur nomogram provided individualized risk estimates for women with DCIS treated with BCS, demonstrating a discriminative ability comparable to that of the MSKCC nomogram.

Project description:ImportanceResidual cancer burden (RCB) distributions may improve the interpretation of efficacy in neoadjuvant breast cancer trials.ObjectiveTo compare RCB distributions between randomized control and investigational treatments within subtypes of breast cancer and explore the relationship with survival.Design, setting, and participantsThe I-SPY2 is a multicenter, platform adaptive, randomized clinical trial in the US that compares, by subtype, investigational agents in combination with chemotherapy vs chemotherapy alone in adult women with stage 2/3 breast cancer at high risk of early recurrence. Investigational treatments graduated in a prespecified subtype if there was 85% or greater predicted probability of higher rate of pathologic complete response (pCR) in a confirmatory, 300-patient, 1:1 randomized, neoadjuvant trial in that subtype. Evaluation of a secondary end point was reported from the 10 investigational agents tested in the I-SPY2 trial from March 200 through 2016, and analyzed as of September 9, 2020. The analysis plan included modeling of RCB within subtypes defined by hormone receptor (HR) and ERBB2 status and compared control treatments with investigational treatments that graduated and those that did not graduate.InterventionsNeoadjuvant paclitaxel plus/minus 1 of several investigational agents for 12 weeks, then 12 weeks of cyclophosphamide/doxorubicin chemotherapy followed by surgery.Main outcomes and measuresResidual cancer burden (pathological measure of residual disease) and event-free survival (EFS).ResultsA total of 938 women (mean [SD] age, 49 [11] years; 66 [7%] Asian, 103 [11%] Black, and 750 [80%] White individuals) from the first 10 investigational agents were included, with a median follow-up of 52 months (IQR, 29 months). Event-free survival worsened significantly per unit of RCB in every subtype of breast cancer (HR-positive/ERBB2-negative: hazard ratio [HZR], 1.75; 95% CI, 1.45-2.16; HR-positive/ERBB2-positive: HZR, 1.55; 95% CI, 1.18-2.05; HR-negative/ERBB2-positive: HZR, 2.39; 95% CI, 1.64-3.49; HR-negative/ERBB2-negative: HZR, 1.99; 95% CI, 1.71-2.31). Prognostic information from RCB was similar from treatments that graduated (HZR, 2.00; 95% CI, 1.57-2.55; 254 [27%]), did not graduate (HZR, 1.87; 95% CI, 1.61-2.17; 486 [52%]), or were control (HZR, 1.79; 95% CI, 1.42-2.26; 198 [21%]). Investigational treatments significantly lowered RCB in HR-negative/ERBB2-negative (graduated and nongraduated treatments) and ERBB2-positive subtypes (graduated treatments), with improved EFS (HZR, 0.61; 95% CI, 0.41-0.93) in the exploratory analysis.Conclusions and relevanceIn this randomized clinical trial, the prognostic significance of RCB was consistent regardless of subtype and treatment. Effective neoadjuvant treatments shifted the distribution of RCB in addition to increasing pCR rate and appeared to improve EFS. Using a standardized quantitative method to measure response advances the interpretation of efficacy.Trial registrationClinicalTrials.gov Identifier: NCT01042379.

Dataset Information

Association of Residual Ductal Carcinoma In Situ With Breast Cancer Recurrence in the Neoadjuvant I-SPY2 Trial.

Importance

Objective

Design, setting, and participants

Interventions

Main outcomes and measures

Results

Conclusions and relevance

Trial registration

Publications

Association of Residual Ductal Carcinoma In Situ With Breast Cancer Recurrence in the Neoadjuvant I-SPY2 Trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets