Multidisciplinary and Tailored Treatment of Locally Advanced Breast Cancer in Progression during Neoadjuvant Chemotherapy: Case Report.

Locally advanced breast cancer (LABC) is a complex disease that requires a multidisciplinary approach. Neoadjuvant chemotherapy (NAC) is usually performed in order to achieve loco-regional radical resection; although its importance in the multidisciplinary approach to LABC is well recognized, a small number of patients show Progressive Disease (PD). No standard salvage treatment (ST) has been defined and different strategies can be adopted, such as second-line systemic therapies, radiation therapy, and surgery. Herein, a case of LABC in PD during NAC is reported with a literature review, with the aim of highlighting the importance of a tailored multidisciplinary treatment for each patient.

Oncoplastic level II volume displacement surgery for breast cancer: oncological and aesthetic outcomes.

Oncoplastic breast-conserving surgery (OBCS) is increasingly used to treat breast cancer with the dual purpose of performing a radical oncological resection while minimizing the risk of post-operative deformities. The aim of the study was to evaluate the patient outcomes after Level II OBCS as regards oncological safety and patient satisfaction. Between 2015 and 2020, a cohort of 109 women consecutively underwent treatment for breast cancer with bilateral oncoplastic breast-conserving volume displacement surgery; patient satisfaction was measured with BREAST-Q questionnaire. The 5-year overall survival and disease-free survival were 97% (95%CI 92, 100) and 94% (95%CI 90, 99), respectively. In two patients (1.8%), mastectomy was finally performed due to margin involvement. The median patient-reported score for "satisfaction with breast" (BREAST-Q) was 74/100. Factors associated with a lower aesthetic satisfaction index included: location of tumour in central quadrant (p = 0.007); triple negative breast cancer (p = 0.045), and re-intervention (p = 0.044). OBCS represents a valid option in terms of oncological outcomes for patients otherwise candidate to more extensive breast conserving surgery; the high satisfaction index also suggests a superiority in terms of aesthetic outcomes.

A Case of Life-Threatening Bleeding Due to a Locally Advanced Breast Carcinoma Successfully Treated with Transcatheter Arterial Embolization.

Locally advanced breast cancer (LABC) may rarely present with acute severe bleeding. A case report dealing with transcatheter arterial embolization to control acute bleeding in a patient with a voluminous ulcerated breast mass is described. Our findings confirm that the endovascular approach is effective in such patients in order to stabilize the patient whenever conventional treatments have failed or bleeding may be life-threatening.

Inferior Pedicle Reduction Mammoplasty as Corrective Surgery after Breast Conserving Surgery and Radiation Therapy.

Background/Aim-Twenty patients had corrective reconstruction surgery by means of a reduction mammaplasty or mastopexy after a previous BCS (Breast Conserving Surgery) and RT (Radiation Therapy); the risk factors and post-operative complications were reported in order to define a safe and effective technique for reduction mammaplasty in previously irradiated breast cancer patients. Materials and Methods-From June 2011 to December 2019, 20 pts. were operated on at the Breast Surgery Clinic of San Martino Policlinic Hospital, Genoa, Italy. Pre- and post-operative parameters included clinic-pathological features of the primary tumor; a lapse of time from primary radio-surgery; the extent of follow-up; the rate of post-operative wound infections; the persistence of breast asymmetry, and a post-operative patient satisfaction index by means of a BREAST-Q questionnaire. Results-Three patients (15%) developed minor complications in the irradiated breast, but no complication was observed into the non-irradiated breast. No statistically significant correlation was found between the post-operative complications and the risk factors. The statistical analysis of BREAST-Q questionnaire responses gave an average patient's satisfaction index that was equal to 90.8/100 (range: 44 to 100). Conclusions-Inferior pedicle reduction mammoplasty is an effective reduction mammoplasty technique in regard to the extent of breast tissues that are to be removed both in irradiated and contralateral breast; moreover, the incidence of post-operative complications is clearly limited when a careful technique is adopted, and it can be reasonably applied also in patients with co-morbidity factors.

"No Ink on Tumor" in Breast-Conserving Surgery after Neoadjuvant Chemotherapy.

Background/Aim: Patients with Stage I-II breast cancer undergoing breast-conserving surgery after neoadjuvant chemotherapy (BCS-NAC) were retrospectively assessed in order to evaluate the extent of a safe excision margin. Materials and Methods: Between 2003 and 2020, 151 patients underwent risk-adapted BCS-NAC; margin involvement was always assessed at definitive histology. Patients with complete pathological response (pCR) were classified as the RX group, whereas those with residual disease and negative margins were stratified as R0 < 1 mm (margin < 1 mm) and R0 > 1 mm (margin > 1 mm). Results: Totals of 29 (19.2%), 64 (42.4%), and 58 patients (38.4%) were included in the R0 < 1 mm, R0 > 1 mm, and RX groups, respectively, and 2 patients with margin involvement had a mastectomy. Ten instances of local recurrence (6.6%) occurred, with no statistically significant difference in local recurrence-free survival (LRFS) between the three groups. A statistically significant advantage of disease-free survival (p = 0.002) and overall survival (p = 0.010) was observed in patients with pCR. Conclusions: BCS-NAC was increased, especially in HER-2-positive and triple-negative tumors; risk-adapted BCS should be preferably pursued to highlight the cosmetic benefit of NAC. The similar rate of LRFS in the three groups of patients suggests a shift toward the "no ink on tumor" paradigm for patients undergoing BCS-NAC.

The Margins' Challenge: Risk Factors of Residual Disease After Breast Conserving Surgery in Early-stage Breast Cancer.

BACKGROUND/AIM: Clinicopathological features of patients undergoing margin enlargement after lumpectomy for early breast cancer with positive/close excision margins were analyzed in order to define whether a re-operative procedure could have been avoided. Furthermore, a standardized protocol of specimen orientation was adopted in order to optimize both the widening procedure as well as the oncologic outcome. PATIENTS AND METHODS: A retrospective analysis was performed including pre-, peri-, and post-operative parameters, and a predictive score by means of a multivariate model was developed using all clinically and statistically significant variables associated with residual disease (RD). RESULTS: RD was significantly related to positive tumor margins, hormone receptor negative, HER2-positive, and tumors with high Ki67 proliferation index (p<0.001); the corresponding contribution to the prognostic score was as follows: close margins, 3 points; hormone receptor positive disease, 2 points; low Ki67, 2 points; HER2 negativity, 1 point. In 102 patients with a score >3, only 2 patients (2.0%) had RD, while in 81 patients with a score ≤3, 55 patients (67.9%) had RD (p<0.001). CONCLUSION: This predictive model might aid in clinical-decision making of patients with positive margins who actually require a widening procedure after intraoperative and/or definitive histology.

Plasma Cell-Free DNA Integrity Assessed by Automated Electrophoresis Predicts the Achievement of Pathologic Complete Response to Neoadjuvant Chemotherapy in Patients With Breast Cancer.

PURPOSE: The study of plasma cell-free DNA integrity (cfDI) has shown potential for providing useful information in neoplastic patients. The aim of this study is to estimate the accuracy of an electrophoresis-based method for cfDI evaluation in the assessment of pathologic complete response (pCR) in patients with breast cancer (BC) undergoing neoadjuvant chemotherapy (NACT). PATIENTS AND METHODS: Fifty-one patients with BC undergoing anthracycline-/taxane-based NACT were recruited. Plasma samples were collected from each patient at diagnosis (t0), after anthracycline administration (t1), and after NACT completion (t2). The concentration of differently sized cell-free DNA fragments was assessed by automated electrophoresis. cfDI, expressed as cfDI index, was calculated as the ratio of 321-1,000 bp sized fragment concentration to 150-220 bp sized fragment concentration assessed at t2. cfDI index was then used to build an exploratory classifier for BC response to NACT, directly comparing its sensitivity and specificity with magnetic resonance imaging (MRI), through bootstrapped logistic regression. RESULTS: cfDI index was assessed on 38 plasma samples collected from as many patients at t2, maintaining a 30/70 ratio between pCR and non-pCR patients. cfDI index showed an area under the receiver operating characteristic curve in predicting the achievement of pCR of 81.6, with a cutoff above 2.71 showing sensitivity = 81.8 and specificity = 81.5. The combination of cfDI index and MRI showed, in case of concordance, an area under the receiver operating characteristic curve of 92.6 with a predictive value of complete response of 87.5 and a predictive value of absence of complete response of 94.7. CONCLUSION: cfDI index measured after NACT completion shows great potential in the assessment of pCR in patients with BC. The evaluation of its use in combination with MRI is strongly warranted in prospective studies.

Relationship between Breast Cancer Surgical Treatment and Psychiatric Symptomatology: Which Sociodemographic and Clinical Factors Could Influence It? A Preliminary Study.

This study aimed to investigate psychiatric symptomatology in a sample of patients affected by breast cancer undergoing surgery, evaluating the potential mediators on perceived stress levels, depression and hopelessness. The study was conducted on eighty-five patients with breast cancer, admitted consecutively to the Breast Unit of the IRCCS Ospedale Policlinico San Martino, between May 2018 and December 2019. Sociodemographic (age of diagnosis, gender, marital and occupational status, educational level, having children) and clinical (type and side of surgery, previous breast surgery, neoadjuvant chemotherapy and axillary dissection) characteristics were investigated through a semi-structured interview. The following rating scales were administered: Beck Depression Inventory, Beck Hopelessness Scale, and Perceived Stress Scale. Our findings indicate that the presence of children and of a partner was associated with a lower total score on the clinical dimensions evaluated. Furthermore, we found demolitive surgery to be a mediator between perceived stress and hopelessness, while history of previous breast surgery was found to be a mediator between demolitive surgery and perceived stress. In conclusion, patients affected by breast cancer undergoing more complex and demolitive surgery or with history of previous breast surgery should be mostly monitored from a psychological and psychiatric point of view from the beginning of treatments to evaluate the first manifestations of psychiatric symptomatology.

Ten Daily Fractions for Whole Breast Cancer Irradiation: Long Term Results.

BACKGROUND/AIM: To report the feasibility and oncological outcomes in breast cancer patients treated with a short hypofractionated radiotherapy schedule. PATIENTS AND METHODS: We evaluated 380 breast cancer patients treated with ten daily fractions of radiotherapy up to 39 Gy on tumor bed. Primary endpoint was local relapse rate (LRR). Secondary endpoints were overall survival (OS) and metastasis-free survival (MFS). RESULTS: The median follow up was 5.0 years. Two- and 5-year LRR rates were 0.2 and 2%, respectively. Two- and 5-year MFS rates were 96.1% and 90.5%, respectively. Two and 5-year OS rates were 97.4% and 95%, respectively. CONCLUSION: This short schedule may represent an alternative option to standard mild hypofractionated radiotherapy in breast cancer patients due to its excellent feasibility and very low recurrence rate.

Breast Cancer Surgery in the COVID-19 Pandemic: Validation of a Preventive Program for Patients and Health Care Workers.

BACKGROUND/AIM: The perspective validation of a selective approach in patients undergoing breast cancer surgery was performed in order to assess whether patients as well as Health Care Workers (HCWs) were exposed to any undue risk of COVD-19 infection. PATIENTS AND METHODS: From March 9th to June 9th 2020, 207 patients were phone-triaged by a dedicated Breast Care Nurse; a patient-tailored program was adopted with the aim of avoiding hospitalization of SARS-CoV-2 symptomatic patients, with a careful prioritization of surgical procedures according to specific disease features. RESULTS: Two hundred and three out of 207 patients underwent operation; seven patients were temporarily excluded because they tested positive at phone triage (n=3), or in-hospital triage (n=3); another asymptomatic patient with negative NP swab tested IgM Ab-positive so that surgery was re-scheduled two weeks later. Four patients had no surgery; one of them was reconsidered for neoadjuvant chemotherapy (NAC) after testing positive at phone triage; three patients were excluded because they were already hospitalized for COVID-19. Overall, mean in-hospital stay was 2.2 days (±SD, 0.7) and, after hospital discharge, no patient required readmission. CONCLUSION: This preventive program avoided any COVID-19 infection among patients and HCWs, so that an elective breast cancer surgical procedure can be safely and timely pursued without affecting the oncologic outcome.

Development of a hoRizontal data intEgration classifier for NOn-invasive early diAgnosis of breasT cancEr: the RENOVATE study protocol.

INTRODUCTION: Standard procedures aimed at the early diagnosis of breast cancer (BC) present suboptimal accuracy and imply the execution of invasive and sometimes unnecessary tissue biopsies. The assessment of circulating biomarkers for diagnostic purposes, together with radiomics, is of great potential in BC management. METHODS AND ANALYSIS: This is a prospective translational study investigating the accuracy of the combined assessment of multiple circulating analytes together with radiomic variables for early BC diagnosis. Up to 750 patients will be recruited at their presentation at the Diagnostic Senology Unit of Ospedale Policlinico San Martino (Genoa, IT) for the execution of a diagnostic biopsy after the detection of a suspect breast lesion (t0). Each recruited patient will be asked to donate peripheral blood and urine before undergoing breast biopsy. Blood and urine samples will also be collected from a cohort of 100 patients with negative mammography. For cases with histological diagnosis of invasive BC, a second sample of blood and urine will be collected after breast surgery. Circulating tumour DNA, cell-free methylated DNA and circulating proteins will be assessed in samples collected at t0 from patients with stage I-IIA BC at surgery together with those collected from patients with histologically confirmed benign lesions of similar size and from healthy controls with negative mammography. These analyses will be combined with radiomic variables extracted with freeware algorithms applied to cases and matched controls for which digital mammography is available. The overall goal of the present study is to develop a horizontal data integration classifier for the early diagnosis of BC. ETHICS AND DISSEMINATION: This research protocol has been approved by Regione Liguria Ethics Committee (reference number: 2019/75, study ID: 4452). Patients will be required to provide written informed consent. Results will be published in international peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT04781062.

Breast Cancer Surgery During the COVID-19 Pandemic: An Observational Clinical Study of the Breast Surgery Clinic at Ospedale Policlinico San Martino - Genoa, Italy.

BACKGROUND: COVID-19 pandemic required a marked re-allocation of healthcare resources, including at Breast Units. A patient-tailored program was developed to assess its efficacy regarding prevention of COVID-19 infection among patients with breast cancer undergoing surgery and healthcare workers (HCWs). PATIENTS AND METHODS: From March 9th to April 9th 2020, 91 patients were selected for elective surgery by means of: i) Pre-hospital screening aimed at avoiding hospitalization of symptomatic or suspicious COVID-19 patients, and ii) prioritisation of surgical procedure according to specific disease features. RESULTS: Eighty-five patients (93.4%) were fit for surgery, while five patients (5.5%) were temporarily excluded through 'telephone triage'; another two patients were excluded at in-hospital triage. A total of 71 out of 85 patients (83.5%) were diagnosed with invasive cancer, most of whom were undergoing breast-conserving surgery (61 out of 85 patients, 71.8%). The mean in-hospital stay was 2.2 days (SD=0.7 days). After hospital discharge, no patient needed re-admission due to post-operative complications; moreover, no COVID-19 infection among patients or HCWs was detected. CONCLUSION: Safe breast cancer surgery was accomplished for both patients and HCWs by means of a careful preoperative selection of patients and in-hospital preventative measures. This screening program can be transferred to high-volume Breast Units and it may be useful in implementing European Community recommendations for prevention of COVID-19 infection.

Tumor-to-nipple Distance Should Not Preclude Nipple-sparing Mastectomy in Breast Cancer Patients. Personal Experience and Literature Review.

BACKGROUND/AIM: A retrospective study was performed in 246 breast cancer patients to define whether tumor-to-nipple distance (TND) assessment by breast MRI may select patients eligible to nipple-sparing mastectomy (NSM) as compared to permanent section assessment of retroareolar margin. PATIENTS AND METHODS: Pre- and post-operative parameters including imaging data, histology of the primary tumor, biologic prognostic factors, and adjuvant regimens were retrieved; patients with close/positive retroareolar margins underwent nipple or NAC excision. The primary endpoint was loco-regional recurrence (LRR). RESULTS: Patients with TND ≤2 cm had a significantly higher rate of invasive ductal carcinoma (p<0.003) and excision margins less than 2 mm (p<0.000). Eleven retroareolar specimens were positive at definitive pathology; final re-excision specimen examination showed residual disease in seven patients (63.6%). At a median follow-up of 31 to 33 months, no NAC recurrence did occur; disease-free survival was more than 96%, and LRR was homogeneously distributed among TND subgroups. CONCLUSION: Therapeutic NSM is a safe procedure independently of TND assessed at preoperative breast MRI. Permanent section assessment of retroareolar tissue is more accurate and cost-effective than frozen section. Furthermore, delayed nipple and/or NAC excision did not impair local disease control.

Circulating Tumor DNA Using Tagged Targeted Deep Sequencing to Assess Minimal Residual Disease in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy.

In breast cancer patients undergoing neoadjuvant chemotherapy before surgery, there is an unmet need for noninvasive predictive biomarkers of response. The analysis of circulating tumor DNA (ctDNA) in particular has been the object of several reports, but few of them have studied the applicability of tagged targeted deep sequencing (tTDS) to clinical practice and its performance compared with droplet digital PCR (ddPCR). Here, we present the first results from an ongoing study involving a prospectively accrued, monocentric cohort of patients affected by invasive breast cancer, undergoing neoadjuvant chemotherapy followed by surgery with curative intent as per clinical practice. A pretreatment tumor biopsy and plasma samples were collected before and during treatment, after surgery, and every six months henceforth or until relapse, whichever came first. Pretreatment biopsies were sequenced with a 409-gene massive parallel sequencing (MPS) panel, allowing the identification of target mutations and their research in plasma by tTDS and ddPCR as a complementary approach. Using tTDS, we demonstrated the presence of at least one deleterious mutation in all the relapsed cases we studied (n = 4), with an average lead time of six months before clinical relapse. The association with ddPCR was suboptimal, and only one relapsed patient could be identified with such method. tTDS shows potential as an early noninvasive method for the detection of MRD in BC patients.

The Role of Sentinel Lymph Node Biopsy in Patients With B5c Breast Cancer Diagnosis.

BACKGROUND/AIM: The histopathological assessment of the B5c category may sometimes be hampered by simple artifacts that may lead to over- or underestimation of that particular breast cancer so that its management is still controversial, especially with regard to the decision to proceed immediately to sentinel lymph node (SLN) biopsy. Hence, a retrospective study was performed in 174 patients undergoing breast-conserving surgery with a preoperative diagnosis of B5c in order to assess the usefulness of axillary node staging by means of SLN biopsy. PATIENTS AND METHODS: Pre- and post-operative parameters including imaging data, histology of the primary tumor and SLN biopsy, biological prognostic factors, type of operation, and adjuvant regimens were computed. RESULTS: Invasive carcinoma and carcinoma in situ were diagnosed in 46 (26.5%) and 128 patients (73.5%), respectively. Preoperative tumor size was significantly related to post-operative diagnosis of invasive carcinoma (p=0.020), retaining its predictive value at logistic regression analysis (p=0.046). Post-operative predictive factors of invasion were represented by tumor stage (p=0.008) and grading (p=0.008). CONCLUSION: B5c preoperative diagnosis in patients undergoing breast conservative surgery would suggest an immediate wide local excision avoiding any further preoperative histologic assessment. Conversely, one-stage SLN biopsy might be suggested for patients eligible to mastectomy, similar to patients with carcinoma in situ, although its impact on the therapeutic and prognostic assessment seems negligible.

Development of a predictor of one-year mortality in older patients with cancer by geriatric and oncologic parameters.

OBJECTIVES: More than 60% of the new cancer diagnoses are currently made in older adults, a highly heterogeneous population. Reliable and time-saving tools to define older adults' prognosis are needed to inform the oncologist's decisions in routine clinical practice. We sought to define a multi-domain classification tool for the prediction of all-cause one-year mortality in a cohort of older adults with solid tumors. MATERIALS AND METHODS: We conducted a single-centre, prospective study of patients with solid cancer aged 65 or older and with G8 score ≤ 14. All patients underwent a comprehensive geriatric assessment (CGA) before starting their surgical or medical treatment. One-year mortality was recorded. A CGA-based prediction tool of one-year mortality was developed and subsequently validated in two independent training and testing cohorts with a 70/30 split, respectively. RESULTS: 162 patients were enrolled. Mean patient age was 78 ±â€¯5.5 years. Forty-three percent of the patients were men. Colorectal and breast cancer were the most common diagnoses. The clinical variables selected for the development of the new classifier (MetaGENUA®) were: mini-nutritional assessment (MNA), instrumental day life activities (IADL), Cumulative Illness Rating Scale (CIRS), geriatric depression scale (GDS), age, and cancer stage. In our independent validation cohort, MetaGENUA® showed high specificity (0.86) and AUC = 0.71 (95% CI = 0.55-0.87). CONCLUSIONS: MetaGENUA® predicts one-year mortality in older patients with cancer with high specificity. As such, MetaGENUA® is predicted to reveal as a useful tool to guide the oncologist's decisions in clinical practice.

Simultaneous Integrated Boost in Once-weekly Hypofractionated Radiotherapy for Breast Cancer in the Elderly: Preliminary Evidence.

AIM: To evaluate once-weekly hypofractionated radiotherapy in elderly patients affected by early breast cancer, reporting acute and late toxicity profiles, and treatment feasibility. PATIENTS AND METHODS: Fifty patients were treated with a hypofractionated regimen: 28.5±2.5 Gy in five fractions at one fraction weekly. Simultaneous integrated boost (SIB) to the tumor bed in high-risk cases. INCLUSION CRITERIA: patients over 70 years old, pT1-2, N0-1a. Acute and late toxicities were assessed based on Radiation Therapy Oncology Group. RESULTS: The median follow-up was 20 months and the median patient age was 79 years. SIB was added for 22 patients (44%). Grade 3-4 acute cutaneous toxicities were not observed; grade 2 toxicity occurred only in four patients (8%). Late subcutaneous tissue toxicity consisted of grade 2 fibrosis in two patients (4%), grade 1 in five (10%) and grade 0 in 41(85%). CONCLUSION: Limiting fraction numbers with a safer profile may improve the management of breast cancer for the elderly.