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Interval Breast Cancer Versus Screen-Detected Cancer: Comparison of Clinicopathologic Characteristics in a Single-Center Analysis

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Interval Breast Cancer Versus Screen-Detected Cancer: Comparison of Clinicopathologic Characteristics in a Single-Center Analysis Interval Breast Cancer Versus Screen-Detected Cancer: Comparison of Clinicopathologic Characteristics in a Single-Center Analysis Gabriele Bellio,1 Riccardo Marion,1 Fabiola Giudici,2 Sara Kus,3 Maura Tonutti,2,3 Fabrizio Zanconati,2,4 Marina Bortul1,2 Abstract Interval breast cancers (IBC) have been of great concern since breast mammogram screening programs were introduced. We compared IBC to screen-detected cancers (SDC). IBC accounted for one-fifth of all breast cancers diagnosed in women who followed the regional screening program. IBC appeared to be more aggressive than SDC in terms of tumor invasiveness, size, and St Gallen molecular subtype, leading to worse overall and disease-free survival. Background: The introduction of breast screening programs has raised the problem of interval breast cancers (IBC). The aims of this study were to analyze the impact of IBC on the screening program, to compare IBC and screen- detected cancers (SDC), and to identify possible predictors of mortality. Patients and Methods: Patients with breast cancer diagnosed during the regional breast screening program between January 2008 and December 2013 at a single center in Italy were included. Demographic, preoperative, and postoperative data were prospectively collected and retrospectively analyzed. Results: Five hundred thirty-four patients were enrolled; 106 women (19.9%) had IBC and 428 women (80.1%) SDC. IBC presented more aggressive features compared to SDC, such as tumor invasive- ness (95% vs. 85%; P .005), tumor size ( pT2 37% vs. 21%; P .001), grade (G3 39% vs. 17%; P < .001), and St ¼ � ¼ Gallen molecular subtype (triple negative 22% vs. 7%; P < .001), resulting in higher distant recurrence rate (8% vs. 2%; P .009) and worse overall and disease-free survival (P .03 and P .001, respectively). Cox multivariate ¼ ¼ ¼ regression analysis identified St Gallen molecular subtype as the only predictor of mortality in patients with breast cancer (P .03). Conclusion: IBC accounted for one-fifth of all breast cancers diagnosed in women who followed the ¼ regional screening program. Furthermore, IBC appeared to have more aggressive features compared to SDC, leading to worse survival. These worse survivals depended on St Gallen molecular subtype. Introduction death among women.1 The introduction of mammogram The American Cancer Society estimated that in 2016, breast screening allowed breast cancers to be detected at earlier stages,2 cancer would be the first tumor discovered in new cancer cases thus improving patients’ prognosis3 thanks to a breast cancere occurring in women in the United States, causing more than 40,000 related mortality reduction of 26%.4 Moreover, the screening deaths and remaining the second leading cause of cancer-related program led to more favorable tumor characteristics in terms of tumor size, lymph node (LN) involvement, and hormone status.5 1Department of General Surgery Besides this prognostic improvement, the screening program 2Breast Unit 3Department of Radiology raised 2 main problems: overdiagnosis of ductal carcinoma-in-situ 4Department of Histopathology, Azienda Sanitaria Universitaria Integrata di Trieste, and interval breast cancers (IBC).6-9 IBC are defined as in-situ or Italy invasive breast cancers diagnosed after a negative mammographic screening examination and before the next recommended routine 10-12 Address for correspondence: Gabriele Bellio, MD, UCO Chirurgia Generale, Strada di screening mammogram. The literature has demonstrated that Fiume 447, Trieste (TS) 34100, Italy IBC are more aggressive than screen-detected cancers (SDC) in terms E-mail contact: [email protected] of tumor size, LN involvement, grade, and molecular features.10,13-18 1 The aims of this study were to analyze the impact of IBC on the Preoperative Evaluation screening program, to compare IBC and SDC in terms of clinical All patients underwent a mammogram and a breast ultrasound and pathologic characteristics, and to identify possible predictors of (US). The Breast Imaging Reporting and Data System (BI-RADS) mortality in patients with breast cancer diagnosed during the of the American College of Radiology was used to refer to breast screening program period. composition categories and to assessment categories for mammo- gram, US, and magnetic resonance imaging.19 Methods US-guided fine-needle aspiration cytology or stereotactic biopsy This retrospective single-center cohort analysis was conducted on was performed in all suspected breast lesions to obtain a definitive prospectively recorded data extracted from the database of the Breast diagnosis. If certain diagnosis was not reached or if the lesion was > Unit of Trieste, Italy. The database collected all patients with both 3 cm, a US-guided core needle biopsy with molecular subtype benign and malignant breast pathologies since 2004. Data on evaluation was carried out. Patients with high-density breast tissue patients’ follow-up and causes of death were retrieved from the (ie, BI-RADS C and D), breast microcalcifications, lobular breast Computerized Medical Records of the Azienda Sanitaria cancers, and/or tumors > 4 cm underwent magnetic resonance Universitaria Integrata di Trieste. imaging. Patients with triple-negative cancers and/or tumors > 5 cm proceeded to staging contrast-enhanced thoracoabdominal computed Inclusion and Exclusion Criteria tomography, bone scintigraphy, and positron emission tomography. This study included women diagnosed with either ductal Axillary US was always performed before surgery to evaluate LN carcinoma-in-situ and invasive cancer who followed the regional status. If abnormal LNs were found, fine-needle aspiration cytology mammographic screening program in Trieste, involving women was carried out. aged 50 to 69 years assessed biennially between January 2008 and Women with a definitive diagnosis of breast cancer were invited December 2013. to undergo a clinical breast examination with a breast surgeon. Since the regional mammographic screening program started in During the visit, a complete history of the patient was collected, and January 2006, patients diagnosed with cancer in the first biennium a clinical examination of breasts and axillary LNs was performed. (ie, 2006 to 2007, the first prevalence round) were not included in All patients were offered pre- and postoperative psychological this study to reduce the bias due to the more aggressive breast support. cancers diagnosed at the beginning of the screening program. Patients following the screening program between 2014 and 2015 Surgical Procedure were not included in this study in order to not negatively influence All cases were evaluated and analyzed preoperatively during the the ratio between IBC and SDC, because IBC could be diagnosed multidisciplinary meeting of the Breast Unit of Trieste, officially until December 2017. Women who underwent screening recognized by the European Society of Mastology in 2016. mammograms after January 2016 were not included because the Women with high-stage, triple-negative, or human epidermal round is not yet completed. growth factor receptor 2 (HER-2)-positive breast cancers were Patients who had not undergone a screening mammogram within referred to neoadjuvant chemotherapy. The surgical procedure was the previous 2 years and those who had a history of breast cancer decided after evaluating the breast volumeetumor dimension ratio, were excluded. molecular subtype (when available), and patient preference. Patients Women included in this study were divided in 2 groups underwent breast conservation surgery (ie, quadrantectomy) or according to the timing of tumor diagnosis: patients with cancers mastectomy, mainly skin or nipple sparing. Immediate or delayed diagnosed during a screening mammogram were classified as SDC, breast reconstruction was usually carried out by plastic surgeons and those who had cancers diagnosed within the 2 years after a after nonconservative breast surgery. negative screening mammogram were identified as IBC. Patients with clinically negative LNs underwent sentinel LN biopsy. Lymphoscintigraphy was performed the day before surgery Parameters Evaluated in all these patients, and the radioactive axillary sentinel LN was The 2 groups were compared in terms of age, family history of localized by gamma probe. Sentinel LNs touch imprint cytologic breast cancer, breast density at mammogram, tumor type and his- analysis was performed intraoperatively to detect axillary metastases. tology, surgical procedure performed, pT, pN, stage, grade, Ki-67, Women with preoperative LNs involvement or positive sentinel LN molecular subtype according to St Gallen criteria, adjuvant therapy, biopsy proceeded to axillary node dissection. All surgical procedures radiotherapy, and survival. were performed by 2 expert breast surgeons. Overall survival (OS) was calculated from the date of surgery All patients signed informed consent preoperatively for the sur- (or diagnostic biopsy for women without surgery) to the date of last gical procedure and for data collection. follow-up or death from any cause. Disease-free survival (DFS) was calculated from the date of surgery (or diagnostic biopsy for women Postoperative Staging without surgery) to the date of last follow-up or to the date of local Breast cancer stage was defined according to the American Joint or distant metastasis. Deadline of follow-up for survival analysis was Committee on Cancer.20 Tumor type was recorded according to the set to October 2016. World Health Organization classification of breast tumors.21
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