The impact of the COVID-19 pandemic in the clinical assistance to breast cancer patients.

PURPOSE: We aimed to disclose the impact of the pandemic on breast cancer patients in a specialized breast cancer center (BCC). METHODS: A total of 501 breast cancer patients with a first appointment in the BCC from April 1st, 2019 to March 31st, 2021 were divided into four consecutive periods of 6 months. Data from the homologous semesters was compared. Patients with an appointment in the BCC during the study period were eligible for the secondary aim of our study (BCC workload). RESULTS: After the pandemic declaration (period 3), we found a decrease in the referral by screening programs (p = 0.002) and a reduction in the waiting time between the primary care referral and the first BCC appointment (p < 0.001). There were higher rates of palpable axillary nodes (p = 0.001), an increase in N stage 2 and 3 (p = 0.050), and a trend for primary endocrine therapy as the first treatment (p = 0.021) associated with higher rates of complete axillary node dissection (p = 0.030). In period 4, there were more outward diagnoses (p = 0.003) and a higher rate of surgery as the first treatment (p = 0.013). CONCLUSION: COVID-19 pandemic implied a more advanced nodal stage, which may be related to the delay in breast cancer screening.

The effectiveness of a group intervention to facilitate posttraumatic growth among women with breast cancer.

OBJECTIVE: This longitudinal study tested the effectiveness of a group intervention designed to facilitate posttraumatic growth (PTG). METHODS: Sample consisted of 205 women diagnosed with non-metastatic breast cancer who were either assigned to an intervention group (n = 58) or to a control group (n = 147). PTG, challenge to core beliefs, and rumination (intrusive and deliberate) were assessed at baseline (T1), at 6 months (T2), and at 12 months after baseline (T3). RESULTS: Results from the Latent Growth Modeling suggested that participants from the intervention group have higher levels of PTG. The challenge to core beliefs and the intrusive rumination have a moderator role on PTG, since group intervention is also linked to the enhancement of both variables. CONCLUSIONS: Participation in the intervention group increase PTG. Challenge to core beliefs and intrusive rumination are improved by group intervention, which to a certain extent facilitate PTG.

Omission of axillary lymph node dissection in breast cancer patients with micrometastasis or isolated tumor cells in sentinel lymph nodes: a 12-year experience in a tertiary breast unit.

INTRODUCTION: After the IBCSG 23-01 trial, our breast center no longer performed axillary lymph node dissection (ALND) after detection of isolated tumor cells (ITC) or micrometastasis in the sentinel lymph nodes (SLN). A recent study suggested that up to half of the patients with micrometastasis in the SLN could benefit from ALND in terms of disease-free survival (DFS) and overall survival (OS). METHODS: This retrospective, unicentric, study analyzed 261 consecutive cT1-3 cN0 breast cancer patients with ITC or micrometastasis in their SLN. Primary objective was comparison of ALND vs. SLN biopsy (SLNB) with regard to DFS and OS. Secondary objectives included analysis of factors associated with an increased rate of locoregional recurrence (LRR), distant metastasis (DM) and metachronous contralateral breast cancer (MCBC). RESULTS: DFS events occurred in 19 patients (7.3%) and 14 patients died (5.4%). Median follow-up time was 78 months. 251 patients (96.2%) had micrometastasis in their SLN. There was no difference in the OS or DFS of ALND vs. SLNB patients. History of previous contralateral breast cancer and WBI were associated with an increased and decreased rate of LRR, respectively. Larger tumor size was associated with an increased rate of DM. Non-ductal histological types were associated with an increased rate of MCBC. DISCUSSION: Avoiding ALND may be safe in pN1mi/pN0(i+) patients. Besides, we strongly encourage clinicians to develop their own follow-up protocols based on the best available evidence, to rapidly identify and treat breast cancer recurrence.

Quality Indicators Compliance and Survival Outcomes in Breast Cancer according to Age in a Certified Center.

Age as a breast cancer (BC) prognostic factor remains debatable. Several studies have investigated clinicopathological features at different ages, but few make an age group direct comparison. The European Society of Breast Cancer Specialists quality indicators (EUSOMA-QIs) allow a standardized quality assurance of BC diagnosis, treatment, and follow-up. Our objective was to compare clinicopathological features, compliance to EUSOMA-QIs and BC outcomes in three age groups (≤45 years, 46-69 years, and ≥70 years). Data from 1580 patients with staged 0-IV BC from 2015 to 2019 were analyzed. The minimum standard and desirable target on 19 mandatory and 7 recommended QIs were studied. The 5-year relapse rate, overall survival (OS), and BC-specific survival (BCSS) were also evaluated. No meaningful differences in TNM staging and molecular subtyping classification between age groups were found. On the contrary, disparities in QIs compliance were observed: 73.1% in ≤45 years and 46-69 years women vs. 54% in older patients. No differences in loco-regional or distant progression were observed between age groups. Nevertheless, lower OS was found in older patients due to concurrent non-oncological causes. After survival curves adjustment, we underscored evidence of undertreatment impacting BCSS in ≥70 years women. Despite a unique exception-more invasive G3 tumors in younger patients-no age-specific differences in BC biology impacting outcome were found. Although increased noncompliance in older women, no outcome correlation was observed with QIs noncompliance in any age group. Clinicopathological features and differences in multimodal treatment (not the chronological age) are predictors of lower BCSS.

A comprehensive study on surveillance outcomes of a male population followed at a hereditary breast cancer high-risk consultation at a Portuguese tertiary hospital.

INTRODUCTION: Men born with pathogenic/likely pathogenic variants in genes associated with the Hereditary Breast and Ovarian Cancer Syndrome have a higher risk to develop breast cancer and other cancers (such as prostate cancer) and should undergo adequate surveillance protocols in highly specialized Centers. METHODS: A retrospective study was conducted to assess these genetic variants' epidemiological and phenotypical manifestations in male carriers, as well as the efficacy of the surveillance protocol and compliance toward it through a survey. During follow-up, a genetic panel for testing was implemented, the starting age for surveillance was delayed, and the six-month screening interval was extended to annual. RESULTS: A total of 104 men from a tertiary hospital's High-Risk Consultation were included, 102 with positive genetic testing for BRCA1 (n = 31), BRCA2 (n = 55), both BRCA2 and another gene (n = 5), CDH1 (n = 2), CHEK2 (n = 4), NF1 (n = 1), RAD51C (n = 4), and an additional two men with no actionable genetic variant identified. The follow-up period ranged from 1 to 13 years, and only one man developed cancer. Survey responses from 48 men in active surveillance showed that more than half recognizes their carrier status and consequent surveillance impact on their life, including the risk of transmission to offspring, fear of future cancer, meaningful distress, and feeling of injustice. Biannual surveillance was not actively detecting more cancer disease cases, confirming the adequacy of the currently implemented protocol CONCLUSION: With support of Genetics to fulfill the current gaps in high-risk management, the proposed redefinition of surveillance protocol would adapt it to the population needs and concerns.

Differences among a Portuguese cohort of BRCA pathogenic/likely pathogenic variants carriers choosing risk-reducing mastectomy or intensive breast surveillance.

PURPOSE: Women with BRCA1 and BRCA2 (BRCA1/2) pathogenic/likely pathogenic (P/LP) variants have a higher risk to develop breast and ovarian cancer. In structured high-risk clinics, risk-reducing measures are adopted. This study aimed at characterizing these women and identify factors that may have influenced their choice between risk reduction mastectomy (RRM) and intensive breast surveillance (IBS). METHODS: This study reviewed retrospectively 187 clinical records of affected and unaffected women with P/LP variants of the BRCA1/2 genes, from 2007 to 2022, of which 50 chose RRM, while 137 chose IBS. The research focused on personal and family history and tumor characteristics and their relation with the preventive option chosen. RESULTS: Among women with personal history of breast cancer, a higher proportion opted for RRM compared to those asymptomatic (34.2% vs 21.3%, p = 0.049), with younger age determining the option for RRM (38.5 years vs 44.0 years, p < 0.001). Among women with personal history of ovarian cancer, a higher proportion opted for RRM compared to those without that history (62.5% vs 25.1%, p = 0.033), with younger age determining the option for RRM (42.6 years vs 62.7 years, p = 0.009). Women who had bilateral salpingo-oophorectomy were more likely to choose RRM than those who did not (37.3% vs 18.3%, p = 0.003). Family history was not associated with preventive option (33.3% vs 25.3, p = 0.346). CONCLUSIONS: The decision for the preventive option is multifactorial. In our study, personal history of breast or ovarian cancer, younger age at diagnosis, and previous bilateral salpingo-oophorectomy were associated with the choice of RRM. Family history was not associated with the preventive option.

Chest wall perforator flaps for partial breast reconstruction after conservative surgery: Prospective analysis of safety and reliability.

INTRODUCTION: Breast-conserving surgery associated with adjuvant radiotherapy is the state of the art in the surgical treatment of breast cancer. Oncoplastic surgery through dermo-adipose flaps based in perforating arteries (muscle sparing flaps) for partial reconstruction is increasingly used as a good option for avoiding musculocutaneous flaps. In this study we evaluate the outcomes of the use of chest wall perforator flaps in the replacement of partial breast volume. METHODS: A prospective cohort study of female patients that underwent a conservative oncoplastic surgery procedure with partial breast reconstruction using a dermo-adipose flap of perforating arteries of the chest wall was conducted between November 2020 and March 2022 at our centre. Primary outcomes were surgical morbidity, positive margins and reoperation rates. Characteristics associated with the occurrence of complications were further identified. RESULTS: Forty-five patients underwent the procedure of interest during the study period. The mean age was 55 years. The median larger dimension of the tumor was 23 mm. Lateral intercostal artery perforator (LICAP), lateral thoracic artery perforator (LTAP), a combined flap and Anterior Intercostal Artery Perforator/Medial Intercostal Artery Perforator (AICAP)/(MICAP) were performed in 22, 16, 2 and 5 patients, respectively. The mean operative time was 126 min. A total of 9 (20.0%) patients required a reoperation after definitive diagnosis, 4 due to positive margins and 5 due to immediate/early surgical morbidity. CONCLUSIONS: Local perforator flaps in oncoplastic breast-conserving surgery are a good option for immediate reconstruction after conservative surgery, showing low morbidity and favourable outcomes.

360 Health Analysis (H360)-A Comparison of Key Performance Indicators in Breast Cancer Management across Health Institution Settings in Portugal.

BACKGROUND: The increased focus on quality indicators (QIs) and the use of clinical registries in real-world cancer studies have increased compliance with therapeutic standards and patient survival. The European Society of Breast Cancer Specialists (EUSOMA) established QIs to assess compliance with current standards in breast cancer care. METHODS: This retrospective study is part of H360 Health Analysis and aims to describe compliance with EUSOMA QIs in breast cancer management in different hospital settings (public vs. private; general hospitals vs. oncology centers). A set of key performance indicators (KPIs) was selected based on EUSOMA and previously identified QIs. Secondary data were retrieved from patients' clinical records. Compliance with target KPIs in different disease stages was compared with minimum and target EUSOMA standards. RESULTS: A total of 259 patient records were assessed. In stages I, II, and III, 18 KPIs met target EUSOMA standards, 5 met minimum standards, and 8 failed to meet minimum standards. Compliance with KPIs varied according to the type of hospital (particularly regarding diagnosis) and disease stage. Although small differences were found in KPI compliance among institutions, several statistical differences were found among treatment KPIs according to disease stage, particularly in stage III. CONCLUSIONS: This study represents the first assessment of the quality of breast cancer care in different hospital settings in Portugal and shows that, although most QIs meet EUSOMA standards, there is room for improvement. Differences have been found across institutions, particularly between oncology centers and general hospitals, in diagnosis and compliance with KPIs among disease stages. Stage III showed the greatest variability in compliance with treatment KPIs, probably related to the lower specificity of the guidelines in this disease stage.

Total Tumor Load to assist in the decision for additional axillary surgery in the positive sentinel node breast cancer patients.

The Total Tumor Load (TTL) concept has been demonstrated to accurately predict the status of the non-sentinel lymph nodes (NSLN) in breast cancer patients. In 2019, our center implemented the TTL cut-off of 30,000 CK19 mRNA copies/µL as sole criterion for deciding on performing ALND. This retrospective, unicentric, study analyzed 87 cT1-3N0 breast cancer patients treated consecutively in a period of two years and aimed to evaluate the performance of this criterion. Secondary objectives included the comparison of the criterion versus our previous Clinical Decision Rule (CDR) versus ACOSOG Z0011 criteria for avoiding an ALND in proportion of patients spared an ALND and in proportion of patients left with a surgically untreated metastasized axilla. An interim analysis revealed new TTL cut-offs for deciding on performing an ALND. The 30,000 CK19 mRNA copies/µL criterion yielded an area under the ROC Curve (AUC) of 0.849, a false positive (FP) rate of 30.1% and a positive predictive value (PPV) of 38.9%. The 30,000 CK19 mRNA copies/µL criterion spared 58.6% of the patients an ALND versus 41.4% with CDR versus 73.6% with Z0011 and left 0.0% patients with a surgically untreated metastasized axilla versus 21.4% with CDR versus 42.9% with Z0011. The new TTL cut-off of 260,000 CK19 mRNA copies/µL for deciding on an ALND yielded an AUC of 0.753, a FP rate of 13.7% and a PPV of 47.4%. This new criterion spared 78.2% of the study sample an ALND and left 35.7% of metastasized axillae surgically untreated. This study emphasizes the need to find a new balance between locoregional control and the morbidity associated with Berg levels I + II axillary lymph node dissection.

[Impact of lymphadenectomy on axillary recurrence and morbidity of the upper limb in breast cancer patients with negative sentinel node. A prospective randomised study]. / Impacto de la linfadenectomía sobre la recurrencia axilar y la morbilidad del miembro superior en pacientes con cáncer de mama y ganglio centinela negativo. Estudio prospectivo aleatorizado.

INTRODUCTION: To determine the impact of axillary lymphadenectomy on regional recurrence, the overall and disease free survival, and upper limb morbidity in patients with breast cancer and negative sentinel node (SN). PATIENTS AND METHODS: A total of 176 patients with breast cancer and negative SN (pN0(sn)) were either randomised to lymphadenectomy (Group I) or to observation only (Group II). The triple technique was used to identify and remove the SN. Follow-up was carried out every 3 months for the first 3 years, and then every 6 months up to 5 years. Pain, numbness (paresthesia), limitations in shoulder mobility, and arm oedema were recorded. RESULTS: No axillary lymph node recurrence was detected in the patients of Group II after 60 months follow up. The overall and disease free survival was similar in both groups. The proportion of patients with morbidity and who had more than two complications was significantly higher in Group I. CONCLUSIONS: Axillary lymphadenectomy may be avoided in patients with negative SN without compromising lymph node extension studies and the patient treatment results. Axillary lymphadenectomy is associated with a higher morbidity of the upper limb compared to SN biopsy.

Frailty-Independent Undertreatment Negative Impact on Survival in Older Patients With Breast Cancer.

PURPOSE: The management of older adults with breast cancer (BC) remains controversial. The challenging assessment of aging idiosyncrasies and the scarce evidence of therapeutic guidelines can lead to undertreatment. Our goal was to measure undertreatment and assess its impact on survival. METHODS: Consecutive patients with BC aged 70 years or older were prospectively enrolled in 2014. Three frailty screening tools (G8, fTRST, and GFI) and two functional status scales (Karnofsky performance score and Eastern Cooperative Oncology Group Performance Status) were applied. Disease characteristics, treatment options, and causes of mortality were recorded during a 5-year follow-up. In addition, we defined undertreatment and correlated its survival impact with frailty. RESULTS: A total of 92 patients were included in the study. The median age was 77 (range 70-94) years. The prevalence of frailty was discordant (G8, 41.9%; fTRST, 74.2%; GFI, 32.3%). Only 47.8% of the patients had a local disease, probably due to a late diagnosis (73.9% based on self-examination). Thirty-three patients (35.6%) died, of which 15 were from BC. We found a considerably high proportion (53.3%) of undertreatment, which had a frailty-independent negative impact on the 5-year survival (hazard ratio [HR], 5.1; 95% confidence interval [CI], 2.1-12.5). Additionally, omission of surgery had a frailty-independent negative impact on overall survival (HR, 3.9; 95% CI, 1.9-7.9). CONCLUSION: BC treatment in older adults should be individualized. More importantly, assessing frailty (not to treat) is essential to be aware of the risk-benefit profile and the patient's well-informed willingness to be treated. Undertreatment in daily practice is frequent and might have a negative impact on survival, as we report.

Clinical Outcome of Patients Submitted to Liver Resection in the Context of Metastatic Breast Cancer: A Study of a Tertiary Hospital Center.

INTRODUCTION: Breast cancer is the most incident cancer in the world, accounting for 25% of new cancers per year in females. It is the most frequent malignancy in women, being the fifth cause of death from cancer worldwide. Approximately 5 to 10% of patients already present with metastases at diagnosis, and the liver is the site of metastases in half of these cases. Liver metastasis (LM) resection, performed after neoadjuvant systemic treatment, has been reported to increase median overall survival in this population. AIM: The aim of this analysis is to assess the outcomes of patients undergoing breast cancer liver metastasis surgical resection, including impact on survival, compared to patients where metastasectomy was not performed. METHODS: retrospective review of 55 female patients with breast cancer liver metastases, diagnosed and treated in a single tertiary university hospital from January 2011 to December 2016 was performed. RESULTS: In 32/55 patients (58.2%), multi-organ metastases were identified (the most common sites being bone, lungs, and lymph nodes). Of the remaining 23 patients, the liver was the unique metastatic site; thirteen patients had diffuse bilobar hepatic metastases. The remaining ten patients were proposed for surgical treatment; three of them had peritoneal carcinomatosis identified during surgery, and no hepatic metastasectomy was performed. As a result, only seven (12.7%) patients underwent liver metastasectomy. Overall survival was higher in patients who had LM surgery (65 months [Interquartile Range (IQR) 54-120]), in comparison to those diagnosed with diffuse bilobar hepatic metastases (17.5 months [IQR 11-41]), and with those showing concurrent liver and bone metastases (16.5 months [IQR 6-36]) (p = 0.012). In univariable analysis, the latter two groups showed worse overall survival outcomes (Hazard Ratio (HR) = 3.447, 95%CI: 1.218-9.756, p = 0.02 and HR = 3.855, 95% Confidence Interval (CI): 1.475-10.077, p = 0.006, respectively) when compared to patients with LM. CONCLUSION: In our series, patients submitted to metastasectomy had a median overall survival after diagnosis of LM three times greater than the non-operated patients with isolated LM, or concurrent LM and bone metastases (65 vs. 17.5 and 16.5 months, respectively). As is vastly known for colorectal cancer liver metastasis, resection of breast cancer liver metastasis may reduce tumor burden, and therefore may improve patient outcome.

Preoperative localisation techniques in breast conservative surgery: A systematic review and meta-analysis.

The preoperative localisation of non-palpable lesions guided by breast imaging is an important and required procedure for breast-conserving surgery. We conducted a systematic review and meta-analysis of the literature on the comparative impact of different techniques for guided surgical excision of non-palpable breast lesions from reports of clinical or patient-reported outcomes and costs. A literature search of PubMed, ISI, SCOPUS and Cochrane databases was conducted for relevant publications and their references, along with public documents, national and international guidelines, conference proceedings and presentations. From 5720 retrieved articles screened through title and abstract, 5346 were excluded and 374 assessed for full-text eligibility. For data extraction and quality assessment, 49 studies were included. Results of this review demonstrate that Radioactive Seed Localisation (RSL) and Radioactive Occult Lesion Localisation (ROLL) outperform Wire in terms of involved margins and reoperations. Between RSL and ROLL, there is a tendency to favour RSL. Similarly, Clip-guided localisation seems preferred when compared to ROLL, however further studies are needed. In summary, there seems to exist evidence that RSL and ROLL are better than Wire, representing potential alternatives, with a quick learning curve, better scheduling and management issues. Although, for recent techniques, more research is needed in order to achieve the same level of evidence.

Sentinel node total tumour load as a predictive factor for non-sentinel node status in early breast cancer patients - The porttle study.

OSNA is a molecular assay for the detection of sentinel node metastasis. TTL emerged as a concept that seems to accurately predict the status of the NSN. Authors tried to confirm this motion. This is a retrospective and multicentric study that analyzed 2164 patients, 579 of whom had positive SN and completion AD. Logistic regression models were performed in order to identify a suitable cutoff to identify patients who benefit from AD. Univariate and multivariate regression analysis showed a relationship between TTL>30000 and the presence of NSN metastasis (OR 2.84, CI 1.99-4.08, p < 0.001). Logistic regression indicated that the cutoff of 30000 copies/µL better discriminates patients with NSN positivity and allows wide use of these criteria. This cutoff value may safely assist clinicians and patients to decide to proceed or not with an AD.

Neoadjuvant endocrine therapy in breast cancer patients.

HIGHLIGHTS: The overall response rate to neoadjuvant endocrine therapy (NET) was 54.55%.The eight patients proposed to tumour's downstage, after 9.71 months of NET, preserved their breast.In the group which achieved response, 10.28 months was the mean time to accomplish it.Even patients who had the worst outcome only began to suffer latter in the course of therapy.NET can be done beyond the conventional 3-4 months to allow additional downstage of the tumour. BACKGROUND: The aim of this study is to evaluate if the extension of neoadjuvant endocrine therapy (NET), beyond the conventional time, allows additional downstage of the tumour, in order to perform a breast conservative surgery (BCS), and to analyze if it is a good option for long-term control in patients who refuse or are unfit for surgery. PATIENTS AND METHODS: We retrospectively reviewed a database containing all patients treated in our institution with NET. All included patients were post-menopausal with primary local disease. The type of response obtained was assessed using modified RECIST criteria. RESULTS: Thirty-three patients were included. Two patients had tumours with 90% expression of oestrogen receptors and all the others had 100%. The tumour size in the largest diameter was 6.51 cm before treatment and 5.18 cm after. Eighteen patients achieved a partial response after 10.28 months of therapy. Patients that were proposed to downstage the tumour performed 9.71 months of therapy until surgery and all were submitted to BCS. Progression occurred after 27.5 months. CONCLUSION: Endocrine therapy is a feasible option for a longer time to allow additional downstage of the tumour and is a good solution in patients who refuse or are unfit for surgery.

Positive margins prediction in breast cancer conservative surgery: Assessment of a preoperative web-based nomogram.

Margin status of the surgical specimen has been shown to be a prognostic and risk factor for local recurrence in breast cancer surgery. It has been studied as a topic of intervention to diminish reoperation rates and reduce the probability of local recurrence in breast conservative surgery (BCS). This study aims to validate the Dutch BreastConservation! nomogram, created by Pleijhus et al., which predicts preoperative probability of positive margins in BCS. Patients with diagnosis of breast cancer stages cT1-2, who underwent BCS at the Breast Center of São João University Hospital (BC-CHSJ) in 2013-2014, were included. Association and correlation were evaluated for clinical, radiological, pathological and surgical variables. Multivariable logistic regression and ROC curves were used to assess nomogram parameters and discrimination. In our series of 253 patients, no associations were found between margin status and other studied variables (such as age or family history of breast cancer), except for weight (p-value = 0.045) and volume (p-value = 0.012) of the surgical specimen. Regarding the nomogram, a statistically significant association was shown between cN1 status and positive margins (p-value = 0.014). No differences were registered between the scores of patients with positive versus negative margins. Discrimination analysis showed an AUC of 0.474 for the basic and 0.508 for the expanded models. We cannot assume its external validation or its applicability to our cohort. Further studies are needed to determine the validity of this nomogram and achieve a broader view of currently available tools.

The impact of the sentinel node concept on the aesthetic outcome of breast cancer conservative surgery.

BACKGROUND: The sentinel node (SN) concept has brought numerous advantages to women with breast cancer. Sparing axillary node anatomy and physiology may enhance the cosmetic results of breast cancer conservative surgery, either owing to less breast edema or to a better tolerance to the effects of surgery and radiotherapy. Our aim was to compare the cosmetic outcome of two randomized groups of patients, on a subjective and objective basis. METHODS: A consecutive series of breast cancer patients (n = 60) submitted to partial mastectomy plus axillary dissection or partial mastectomy plus SN biopsy (included in a randomized trial) was photographed. Photos were analysed in three ways: by seven different observers according to seven features from poor to excellent; two observers estimated the percentage of breast retraction assessment (pBRA); or by the BCCT.core 1.0(®) software. RESULTS: The panel subjective analysis showed a benefit in terms of the skin colour for the patients submitted to SN biopsy only. This group of patients did not show any advantage in terms of pBRA estimates even after the complex BCCT.core appraisal. CONCLUSIONS: The sentinel node concept is not associated with improvements in the aesthetic outcome of breast cancer conservative treatment.