Evaluating the ability of an artificial-intelligence cloud-based platform designed to provide information prior to locoregional therapy for breast cancer in improving patient's satisfaction with therapy: The CINDERELLA trial.

BACKGROUND: Breast cancer therapy improved significantly, allowing for different surgical approaches for the same disease stage, therefore offering patients different aesthetic outcomes with similar locoregional control. The purpose of the CINDERELLA trial is to evaluate an artificial-intelligence (AI) cloud-based platform (CINDERELLA platform) vs the standard approach for patient education prior to therapy. METHODS: A prospective randomized international multicentre trial comparing two methods for patient education prior to therapy. After institutional ethics approval and a written informed consent, patients planned for locoregional treatment will be randomized to the intervention (CINDERELLA platform) or controls. The patients in the intervention arm will use the newly designed web-application (CINDERELLA platform, CINDERELLA APProach) to access the information related to surgery and/or radiotherapy. Using an AI system, the platform will provide the patient with a picture of her own aesthetic outcome resulting from the surgical procedure she chooses, and an objective evaluation of this aesthetic outcome (e.g., good/fair). The control group will have access to the standard approach. The primary objectives of the trial will be i) to examine the differences between the treatment arms with regards to patients' pre-treatment expectations and the final aesthetic outcomes and ii) in the experimental arm only, the agreement of the pre-treatment AI-evaluation (output) and patient's post-therapy self-evaluation. DISCUSSION: The project aims to develop an easy-to-use cost-effective AI-powered tool that improves shared decision-making processes. We assume that the CINDERELLA APProach will lead to higher satisfaction, better psychosocial status, and wellbeing of breast cancer patients, and reduce the need for additional surgeries to improve aesthetic outcome.

PET/MRI for Staging the Axilla in Breast Cancer: Current Evidence and the Rationale for SNB vs. PET/MRI Trials.

Axillary surgery in breast cancer (BC) is no longer a therapeutic procedure but has become a purely staging procedure. The progressive improvement in imaging techniques has paved the way to the hypothesis that prognostic information on nodal status deriving from surgery could be obtained with an accurate diagnostic exam. Positron emission tomography/magnetic resonance imaging (PET/MRI) is a relatively new imaging tool and its role in breast cancer patients is still under investigation. We reviewed the available literature on PET/MRI in BC patients. This overview showed that PET/MRI yields a high diagnostic performance for the primary tumor and distant lesions of liver, brain and bone. In particular, the results of PET/MRI in staging the axilla are promising. This provided the rationale for two prospective comparative trials between axillary surgery and PET/MRI that could lead to a further de-escalation of surgical treatment of BC. • SNB vs. PET/MRI 1 trial compares PET/MRI and axillary surgery in staging the axilla of BC patients undergoing primary systemic therapy (PST). • SNB vs. PET/MRI 2 trial compares PET/MRI and sentinel node biopsy (SNB) in staging the axilla of early BC patients who are candidates for upfront surgery. Finally, these ongoing studies will help clarify the role of PET/MRI in BC and establish whether it represents a useful diagnostic tool that could guide, or ideally replace, axillary surgery in the future.

Single-cell transcriptomics reveals multi-step adaptations to endocrine therapy.

Resistant tumours are thought to arise from the action of Darwinian selection on genetically heterogenous cancer cell populations. However, simple clonal selection is inadequate to describe the late relapses often characterising luminal breast cancers treated with endocrine therapy (ET), suggesting a more complex interplay between genetic and non-genetic factors. Here, we dissect the contributions of clonal genetic diversity and transcriptional plasticity during the early and late phases of ET at single-cell resolution. Using single-cell RNA-sequencing and imaging we disentangle the transcriptional variability of plastic cells and define a rare subpopulation of pre-adapted (PA) cells which undergoes further transcriptomic reprogramming and copy number changes to acquire full resistance. We find evidence for sub-clonal expression of a PA signature in primary tumours and for dominant expression in clustered circulating tumour cells. We propose a multi-step model for ET resistance development and advocate the use of stage-specific biomarkers.

Oncoplastic breast surgery for the management of ductal carcinoma in situ (DCIS): is it oncologically safe? A retrospective cohort analysis.

BACKGROUND: Few data exist in literature regarding oncoplastic surgery (ONC) and ductal carcinoma in situ (DCIS). The role of ONC in the treatment of DCIS has not been elucidated yet: no case-control study has yet been published on the issue and no long-term oncologic results are reported. METHODS: Using the European Institute of Oncology (IEO) institutional breast cancer data base we investigated the oncologic safety of ONC for DCIS comparing a consecutive series of 44 patients who have underwent ONC followed by external irradiation for DCIS (Group A-study group) with 375 patients who received conservation alone followed by external irradiation for DCIS (Group B control group) in the same period. We excluded patients presenting with secondary tumors or local relapses and those requiring re-excision or completion mastectomy for positive margins. Primary endpoints were disease-free survival (DFS) and ipsilateral breast tumor recurrence (IBTR) within the study group and comparison with the control group. RESULTS: Events rates and death rates were similar in the two groups. The average annual rate of invasive IBTR in group A and B was 1.6% and 1.0% respectively. No difference in the rate of lymphnode metastasis, distant metastasis, contralateral breast cancer, other primary cancer or death was observed across the two groups. CONCLUSIONS: Our findings suggest the safety of ONC and irradiation for the management of DCIS extending the indications for conservation in DCIS patients otherwise treated with mastectomy. It provides the best available evidence supporting ONC as a valid treatment option for the management of DCIS.

Prognostic value of tumour-infiltrating lymphocytes in small HER2-positive breast cancer.

BACKGROUND: The standard treatment for patients with small, node-negative, human epidermal growth factor receptor type 2 (HER2)-positive breast cancer (BC) is still controversial. Our aim was to assess the prognostic role of tumour-infiltrating lymphocytes (TILs) in patients with stage pT1a-b HER2-positive BC. PATIENTS AND METHODS: Haematoxylin and eosin slides from node-negative, pT1a-b HER2-positive BC surgical specimens were retrieved from pathology archives to assess TILs and their association with outcome. RESULTS: TILs were evaluated in 205 patients with HER2-positive, pT1a-b tumours, who underwent breast surgery between 1997 and 2009 at the European Institute of Oncology. At a median follow-up of 11 years, we did not observe any association between the presence of TILs, either assessed as a continuous or dichotomous variable (<50 versus ≥ 50%), and outcome. Within the subgroup of patients with pT1a tumours who did not receive any adjuvant therapy (36/97 patients), the rate of disease-free survival events was lower in lymphocyte-predominant BC (LPBC) as compared with non-LPBC patients (p = 0.066). CONCLUSIONS: TILs cannot be used as a prognostic biomarker in pT1a-b HER2-positive BC. Additional biomarkers are needed for selecting patients with stage I HER2-positive BC who candidate to adjuvant therapy de-escalation.

Memories of paternal relations are associated with coping and defense mechanisms in breast cancer patients: an observational study.

BACKGROUND: Breast cancer diagnosis and treatment represent stressful events that demand emotional adjustment, thus recruiting coping strategies and defense mechanisms. As parental relations were shown to influence emotion regulation patterns and adaptive processes in adulthood, the present study investigated whether they are specifically associated to coping and defense mechanisms in patients with breast cancer. METHODS: One hundred and ten women hospitalized for breast cancer surgery were administered questionnaires assessing coping with cancer, defense mechanisms, and memories of parental bonding in childhood. RESULTS: High levels of paternal overprotection were associated with less mature defenses, withdrawal and fantasy and less adaptive coping mechanisms, such as hopelessness/helplessness. Low levels of paternal care were associated with a greater use of repression. No association was found between maternal care, overprotection, coping and defense mechanisms. Immature defenses correlated positively with less adaptive coping styles, while mature defenses were positively associated to a fighting spirit and to fatalism, and inversely related to less adaptive coping styles. CONCLUSIONS: These data suggest that paternal relations in childhood are associated with emotional, cognitive, and behavioral regulation in adjusting to cancer immediately after surgery. Early experiences of bonding may constitute a relevant index for adaptation to cancer, indicating which patients are at risk and should be considered for psychological interventions.

Feasibility of lymphoscintigraphy for sentinel node identification after neo-adjuvant therapy.

AIM: To assess the sentinel-node identification rate at lymphoscintigraphy and its technical feasibility after neo-adjuvant treatments. MATERIAL OF STUDY: Between 2000 and 2013, 444 consecutive patients affected by primary locally advanced breast cancer were enrolled in this study. All individuals were candidate for neo-adjuvant treatments and for lymphoscintigraphy before surgery. RESULTS: The median age was 44 years at onset; almost one sentinel node was identified during lymphoscintigraphy in 430 cases. The detection rate at lymphoscintigraphy was 96.9% (95% CI, 94.8-98.1%). Considering the correlation between specific treatments and sentinel node identification rate, we verified that the detection rate did not vary significantly (p=0.53) according to the type of neo-adjuvant therapies administered to the patients. CONCLUSIONS: Our results demonstrated that lymphoscintigraphy for sentinel node identification is a safe and feasible procedure after neo-adjuvant therapies, independently of treatment types. KEY WORDS: Breast Cancer, Neo-Adjuvant Treatment, Sentinel lymphnode biopsy, Lymphoscintigraphy.

Comparison of Treatment Outcome Between Invasive Lobular and Ductal Carcinomas in Patients Receiving Partial Breast Irradiation With Intraoperative Electrons.

PURPOSE: To investigate the local outcome of patients after accelerated partial breast irradiation with intraoperative electrons (IORT) for invasive lobular carcinoma (ILC) compared with invasive ductal carcinoma (IDC). METHODS AND MATERIALS: From 1999 to 2007, 2173 patients were treated with breast-conserving surgery and IORT (21 Gy/1 fraction) as the sole local treatment: 252 patients with ILC (11.6%) were compared with 1921 patients with IDC in terms of local control. RESULTS: Compared with the IDC subgroup, patients with ILC had a low-risk profile and were more hormone responsive. The 5- and 10-year in-breast tumor reappearance (IBTR) rates were 5.5% and 14.4%, respectively, for the IDC group and 7.5% and 21.8%, respectively, for the ILC group (log-rank P=.03). The excess risk of IBTR associated with ILC was particularly high for small tumors (≤1 cm: hazard ratio [HR], 2.24; 95% confidence interval [CI], 1.03-4.85), elderly patients (60-69 years: HR, 2.27; 95% CI, 1.11-4.63; ≥70 years: HR, 3.28; 95% CI, 1.08-10.0), low-grade tumors (grade 1: HR, 3.50; 95% CI, 1.05-11.7), and luminal A molecular subtype (HR, 3.18; 95% CI, 1.49-6.77). Among the ILC histologic variants, no difference between classic and nonclassic subgroups was observed, although the signet ring cell and solid variants had the worst local control. CONCLUSIONS: Despite a favorable tumor profile, accelerated partial breast irradiation with IORT led to a higher incidence of IBTRs in patients with ILC compared with those with IDC. Our institutional experience emphasized the importance of the size of the irradiation field, pointing to the use of larger collimators, even when dealing with small tumors, to improve local control.

Metabolic shifts in residual breast cancer drive tumor recurrence.

Tumor recurrence is the leading cause of breast cancer-related death. Recurrences are largely driven by cancer cells that survive therapeutic intervention. This poorly understood population is referred to as minimal residual disease. Here, using mouse models that faithfully recapitulate human disease together with organoid cultures, we have demonstrated that residual cells acquire a transcriptionally distinct state from normal epithelium and primary tumors. Gene expression changes and functional characterization revealed altered lipid metabolism and elevated ROS as hallmarks of the cells that survive tumor regression. These residual cells exhibited increased oxidative DNA damage, potentiating the acquisition of somatic mutations during hormonal-induced expansion of the mammary cell population. Inhibition of either cellular fatty acid synthesis or fatty acid transport into mitochondria reduced cellular ROS levels and DNA damage, linking these features to lipid metabolism. Direct perturbation of these hallmarks in vivo, either by scavenging ROS or by halting the cyclic mammary cell population expansion, attenuated tumor recurrence. Finally, these observations were mirrored in transcriptomic and histological signatures of residual cancer cells from neoadjuvant-treated breast cancer patients. These results highlight the potential of lipid metabolism and ROS as therapeutic targets for reducing tumor recurrence in breast cancer patients.

Fat Grafting after Invasive Breast Cancer: A Matched Case-Control Study.

BACKGROUND: Fat grafting has been widely indicated for postmastectomy and postlumpectomy breast reconstruction. The literature emphasizes the clinical efficacy of fat grafting, but experimental studies raise important questions about the recurrence risk because of the stimulation of remaining cancer cells by progenitor or adult adipocytes. Because breast conservative treatment provides a higher risk of residual cancer cells in the breast tissue compared with mastectomy, the authors set up a matched case-control study of fat grafting versus no fat grafting after breast conservative treatment. METHODS: The authors collected data from 322 consecutive patients operated on for a primary invasive breast cancer who subsequently underwent fat grafting for breast reshaping from 2006 to 2013. All patients were free of recurrence before fat grafting. For each patient, the authors selected one patient with similar characteristics who did not undergo fat grafting. RESULTS: After a mean follow-up of 4.6 years (range, 0.1 to 10.2 years) after fat grafting, or a corresponding time for controls, the authors observed no difference in the incidence of local events (fat grafting, n = 14; controls, n = 16; p = 0.49), axillary nodes metastasis (fat grafting, n = 3; controls, n = 6; p = 0.23), distant metastases (fat grafting, n = 14; controls, n = 15; p = 0.67), or contralateral breast cancer (fat grafting, n = 4; controls, n = 4; p = 0.51). CONCLUSION: Fat grafting seems to be a safe procedure after breast conservative treatment for breast cancer patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Ipsilateral axillary recurrence after breast conservative surgery: The protective effect of whole breast radiotherapy.

BACKGROUND AND PURPOSE: Whole breast radiotherapy (WBRT) is one of the possible reasons for the low rate of axillary recurrence after breast-conserving surgery (BCS). PATIENTS AND METHODS: We retrospectively collected data from 4,129 consecutive patients with breast cancer ⩽2cm and negative sentinel lymph node who underwent BCS between 1997 and 2007. We compared the risk of axillary lymph node recurrence between patients treated by WBRT (n=2939) and patients who received partial breast irradiation (PBI; n=1,190) performed by a single dose of electron intraoperative radiotherapy. RESULTS: Median tumour diameter was 1.1cm in both WBRT and PBI. Women who received WBRT were significantly younger and expressed significantly more multifocality, extensive in situ component, negative oestrogen receptor status and HER2 over-expression than women who received PBI. After a median follow-up of 8.3years, 37 and 28 axillary recurrences were observed in the WBRT and PBI arm, respectively, corresponding to a 10-year cumulative incidence of 1.3% and 4.0% (P<0.001). Multivariate analysis resulted in a hazard ratio of 0.30 (95% CI 0.17-0.51) in favour of WBRT. CONCLUSIONS: In this large series of women with T1 breast cancer and negative sentinel lymph node treated by BCS, WBRT lowered the risk of axillary recurrence by two thirds as compared to PBI.

Benefit of low-dose tamoxifen in a large observational cohort of high risk ER positive breast DCIS.

Low-dose tamoxifen has comparable antiproliferative effect to the standard dose of 20 mg/day in biomarker trials, but its clinical efficacy remains unclear. We assessed the effect of low-dose tamoxifen on ipsilateral recurrence in ductal carcinoma in situ (DCIS) patients treated in a referral Institution between 1996 and 2008. Following conserving surgery, women received radiotherapy and/or low-dose tamoxifen upon clinical judgment and patient preferences. Cox regression analyses were used with and without confounding factors. Among 1,091 women with DCIS and median age 53 years (IQR: 46-62), 544 (49.9%) received radiotherapy. Of the 833 women with oestrogen receptor (ER) positive DCIS, 467 (56.1%) received low-dose tamoxifen. After a median of 7.7 years, 235 ipsilateral recurrences and 62 contralateral breast tumors were observed. Low-dose tamoxifen significantly decreased any breast event (HR = 0.70, 95% CI: 0.54-0.91) and ipsilateral DCIS recurrence (HR = 0.66, 95% CI: 0.49-0.88), but not ipsilateral invasive recurrence or contralateral tumors. Radiotherapy showed a large significant reduction for any breast event (HR = 0.55, 95% CI: 0.42-0.72). Tamoxifen was more effective on all breast events in women aged >50 years than in women aged ≤50 (HR = 0.51, 95% CI: 0.33-0.77 versus HR = 0.84, 95% CI: 0.60-1.18, p-interaction = 0.03). Age ≤50 years, positive margins, high Ki67, high grade and low BMI were independent predictors of ipsilateral recurrence. No increase of endometrial cancers and fewer deaths (p = 0.015) were observed on tamoxifen. Low-dose tamoxifen seems to be safe and effective in reducing ipsilateral recurrence in ER positive DCIS in women aged >50 years. A randomized trial is underway to confirm these findings.

HER2 Equivocal Status in Early Breast Cancer Is Not Associated with Higher Risk of Recurrence.

AIM: The primary aim of the study was to assess the association between risk of recurrence and HER2 equivocal gene status through immunohistochemistry in patients with early breast cancer. PATIENTS AND METHODS: We retrospectively analyzed clinical and pathological data of 455 consecutive patients with early breast cancer (BC) who were HER2(+) and had a HER2/CEP17 ratio <2.0, who underwent surgery at the European Institute of Oncology after 2007. The role of HER2/CEP17 ratio on recurrence-free survival was assessed with univariate and multivariate Cox regression models. RESULTS: We found no significant association between risk of recurrence and HER2 equivocal testing in patients with early breast cancer. In subgroup analysis, a significant interaction between HER2/CEP17 ratio and nodal involvement was observed (p=0.02). CONCLUSION: Patients with HER2 equivocal status have no significantly higher risk of recurrence.

Impact of autoimmune diseases on outcome of patients with early breast cancer.

Our aim was to analyze the impact of a concurrent autoimmune disease on outcome of patients with early breast cancer. We reviewed medical charts of patients with a diagnosis of autoimmune diseases (AD) among a population of 17.153 cases. We categorized ADs as endocrine, rheumatic, systemic, neurological diseases and vasculitis. For each patient in the study group, we matched 2 patients. The events to determine overall survival (OS) and disease free survival (DFS) were identified from follow-up data. We identified 279 (1.62%) patients with early breast cancer and concurrent ADs. The median follow-up was 7.0 years. The 10-year OS rate was 86% (95% CI, 80% to 91%) in the study group and 90% (95% CI, 86% to 93%) for the control group (p = 0.011). In patients with ER positive/HER2 negative subtype a worse OS was observed in the study group when compared to the control group (p = 0.0046); this difference remained statistically significant when the analysis was restricted to breast cancer mortality (p = 0.045). The 10-year DFS rate was 69% (95% CI, 61% to 76%) in the study group and 72% (95% CI, 66% to 77%) for the control group (p = 0.22). Autoimmunity at diagnosis of early breast cancer is associated with worse survival.

Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination.

Chronic stress induces signalling from the sympathetic nervous system (SNS) and drives cancer progression, although the pathways of tumour cell dissemination are unclear. Here we show that chronic stress restructures lymphatic networks within and around tumours to provide pathways for tumour cell escape. We show that VEGFC derived from tumour cells is required for stress to induce lymphatic remodelling and that this depends on COX2 inflammatory signalling from macrophages. Pharmacological inhibition of SNS signalling blocks the effect of chronic stress on lymphatic remodelling in vivo and reduces lymphatic metastasis in preclinical cancer models and in patients with breast cancer. These findings reveal unanticipated communication between stress-induced neural signalling and inflammation, which regulates tumour lymphatic architecture and lymphogenous tumour cell dissemination. These findings suggest that limiting the effects of SNS signalling to prevent tumour cell dissemination through lymphatic routes may provide a strategy to improve cancer outcomes.

Use of beta-blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and breast cancer survival: Systematic review and meta-analysis.

Breast cancer (BC) is the second leading cause of cancer death among women in Western Countries. Beta-blocker (BB) drugs, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) were suggested to have a favorable role in the development and progression of BC. We have performed a meta-analysis to clarify the potential benefits of these drugs on BC survival. A total number of 46 265 BC patients from eleven papers were included, ten independent studies on BB use and seven on ACEi/ARB use. The summary hazard ratio (SHR) was estimated by pooling the study-specific estimates with random effects models and maximum likelihood estimation. We assessed the homogeneity of the effects across studies and evaluated between-study heterogeneity by meta-regression and sensitivity analyses. We found a significant improvement in BC specific survival for patients treated with BB drugs at the time of BC diagnosis (SHR: 0.44; 95%CI: 0.26-0.73 with I(2) = 78%). We also observed a borderline significant improvement in disease free survival for subjects treated with BB (SHR: 0.71, 95%CI: 0.19-1.03). No association of ACEi/ARB use with disease free and overall survival was found. In conclusion, we report epidemiological evidence that BB improve BC-specific survival. Clinical trials addressing this hypothesis are warranted.

Oncoplastic Breast-Conserving Surgery for Tumors Larger than 2 Centimeters: Is it Oncologically Safe? A Matched-Cohort Analysis.

BACKGROUND: Oncoplastic surgery is a well-established approach that combines conserving treatment for breast cancer and plastic surgery techniques. Although this approach has been described for T2 tumors, no long-term oncologic follow-up and no comparison with patients undergoing mastectomy has been published. The purpose of the study was to demonstrate that oncoplastic surgery is a safe and reliable treatment for managing invasive primary T2 breast cancer. METHODS: We compared a consecutive series of 193 T2 patients who have undergone oncoplastic surgery (study group) with 386 T2 patients who have undergone mastectomy (control group). The endpoints evaluated were disease-free survival (DFS), overall survival (OS), cumulative incidence of local recurrence (CI-L), regional recurrence (CI-R), and distant recurrence (CI-D), all measured from the date of surgery. RESULTS: Median follow-up is 7.4 years. The OS is similar within the two groups: 87.3 and 87.1 % at 10 years in the ONC group and control group, respectively (p value, adjusted for multifocality and tumor size, 0.74). Also, the DFS is similar in both groups: 60.9 and 56.3 % at 10 years in the ONC group and control group, respectively. The incidence of local events is slightly higher in the oncoplastic group, whereas the incidence of regional events is slightly higher in the mastectomy group. These differences are not statistically significant. The cumulative incidence of distant events is similar within the two groups. CONCLUSIONS: To our knowledge, the present study provides the best available evidence to suggest that oncoplastic approach is a safe and reliable treatment for managing invasive pT2 breast cancers.

Stress Exposure in Significant Relationships Is Associated with Lymph Node Status in Breast Cancer.

OBJECTIVE: Life stress exposure may impact on health and disease. Previous literature showed that stressful life events are associated with cancer incidence, survival and mortality. In animal models, patterns of maternal care have been shown to critically affect stress sensitivity and immunity trajectories later in life, by modifying DNA methylation during critical periods early in life. However, the role of parental care in breast cancer progression and survival has only limitedly been explored. Here, we investigated whether these factors may be linked to biological prognostic variables. METHODS: One hundred twenty-three women hospitalized for surgery of primary breast cancer completed a questionnaire assessing parental bonding. Stressful events throughout the life span were also assessed. RESULTS: We found that the absence of optimal parental relationships is significantly associated with an increased risk of lymph node involvement, adjusting for confounders, while cumulative stress in the area of sentimental relationships is borderline significantly associated with the same prognostic factor. CONCLUSIONS: Our results suggest that parental bonding and sentimental relations may have a role in breast cancer progression. These variables represent an important evolutionary aspect which may modulate cancer progression through psycho-physiological stress pathways and influence the immune system.

Outcome and Medial Presentation of Breast Cancer: European Institute of Oncology Experience.

BACKGROUND: No analyses have investigated the prognostic role of medial presentation in breast cancer patients on disease-free survival (DFS) and overall survival according to immunohistochemically-defined subtypes. PATIENTS AND METHODS: We collected information from the institutional clinical database on consecutive breast cancer patients who underwent conservative surgery at the European Institute of Oncology, Milan, Italy, between 1994 and 2008. We compared the outcomes of patients with medial breast cancer with those of patients with nonmedial tumors observed at the institution during the same period. RESULTS: Among 7369 evaluable patients, 2254 (24%) had their primary tumors in medial quadrants and 7015 (76%) in other areas. Five-year DFS was 84.7% and 86.6% (P = .008) in patients with medial and nonmedial disease, respectively. In multivariate analysis, medial location was correlated with greater risk of recurrence (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.11-1.35; P < .0001) and death (HR, 1.27; 95% CI, 1.09-1.49; P = .0028). CONCLUSION: Medial presentation is an adverse prognostic factor for breast cancer patients.