Management Of Early Breast Cancer Research Articles

The case against IORT in the management of early stage breast cancer

Since the development of breast conserving therapy (BCT) that incorporated standard fractionation whole breast irradiation (WBI) delivered daily over 5–7 weeks, there has been a concerted effort to shorten the duration of adjuvant radiation therapy as a way to improve convenience and compliance, reduce costs, and potentially reduce toxicities. Over the past decade, an unprecedent shift in breast radiation techniques and regimens has led to the emergence of shorter courses of WBI (5–15 fractions) as well as partial breast approaches which also reduce treatment duration to 1–3 weeks.

Optimizing Preventive Adjuvant Linac-Based (OPAL) Radiation: A Phase 2 Trial of Daily Partial Breast Irradiation

Evidence supports use of partial-breast irradiation (PBI) in the management of early breast cancer, but the optimal dose-fractionation remains unsettled. We conducted a phase 2 clinical trial (OPAL trial) to evaluate a novel PBI dosing schedule of 35 Gy in 10 daily fractions. Patients with close (<2 mm) margins also received a boost of 9 Gy in 3 fractions. Eligible patients underwent margin-negative lumpectomy for ductal carcinoma in situ or estrogen receptor-positive invasive breast cancer, up to 3 cm, pTis-T2 N0. The primary outcome was any grade ≥2 toxic effect occurring from the start of radiation through 6 months of follow-up. Secondary outcomes included patient-reported cosmesis, breast pain, and functional status, measured using the Breast Cancer Treatment Outcomes Scale, and physician-reported cosmesis, measured using the Radiation Therapy and Oncology Group scale. The Cochran-Armitage trend test and multivariable mixed-effects longitudinal growth curve models compared outcomes for the OPAL study population with those for a control group of similar patients treated with whole-breast irradiation (WBI) plus boost. All 149 patients enrolled on the OPAL trial received the prescribed dose, and 17.4% received boost. The median age was 64 years; 83.2% were White, and 73.8% were overweight or obese. With median follow-up of 2.0 years, 1 patient (0.7%) experienced in-breast recurrence. Prevalence of the primary toxicity outcome was 17.4% (26 of 149 patients) in the OPAL trial compared with 72.7% (128 of 176 patients) in the control WBI-plus-boost cohort (P < .001). In longitudinal multivariable analysis, treatment on the OPAL trial was associated with improved patient-reported cosmesis (P < .001), functional status (P=.004), breast pain (P=.004), and physician-reported cosmesis (P < .001). Treatment with daily PBI was associated with substantial reduction in early toxicity and improved patient- and physician-reported outcomes compared with WBI plus boost. Daily external-beam partial-breast irradiation with 13 or fewer fractions merits further prospective evaluation.

Short term recurrence and survival rate of breast cancer patients post surgical treatment; north borneo experience

IntroductionBreast cancer is the most common cancer among women and one of the major causes of mortality and morbidity worldwide. The aim of this study is to determine two-year cumulative recurrence rates and survival rates and their influential factors among women with breast cancer after surgical treatment. MethodsThe breast cancer registry with focus on patient's outcome after treatment was retrospectively review for relevant data. The study was started on 2019. All breast cancer patients who underwent surgical procedure between 2016 and 2019 were identified and recruited in this study and was follow up for two year. We performed Kaplan Meier method to determine 2-year recurrence rates and survival rates and compared unadjusted survival statistics using Log-rank test between baseline variables and outcomes. ResultFrom 2016 to 2019, a total of 482 breast cancer patients underwent surgical procedure. The overall observed 2-year recurrence rate among breast cancer patients after surgical treatment was 11.8% (95%CI:8.5,16.4) while for the survival rate was 94.8% (95% CI:91.8,96.7). Log rank test showed that lymph node involvement (p < 0.001) and high lymph node ratio (p < 0.001) were associated with higher cumulative recurrence rates. Meanwhile, stage 4 breast cancer (p = 0.001), higher grade tumour (p = 0.011), larger tumour size (>5 cm) (P = 0.005) and type of tumour (p = 0.018) were demonstrated to have lower survival rates. ConclusionRecurrence rate were significant predictor among patient with lymph node involvement and higher lymph node ratio, while stages of tumour, tumour grade, size of tumour and type of tumour were all highly significant predictor for survival rate. Therefore, the aim for early diagnosis and management of breast cancer is crucial in improving the treatment outcome.

RNA sequencing-based single sample predictors of molecular subtype and risk of recurrence for clinical assessment of early-stage breast cancer

Multigene assays for molecular subtypes and biomarkers can aid management of early invasive breast cancer. Using RNA-sequencing we aimed to develop single-sample predictor (SSP) models for clinical markers, subtypes, and risk of recurrence (ROR). A cohort of 7743 patients was divided into training and test set. We trained SSPs for subtypes and ROR assigned by nearest-centroid (NC) methods and SSPs for biomarkers from histopathology. Classifications were compared with Prosigna in two external cohorts (ABiM, n = 100 and OSLO2-EMIT0, n = 103). Prognostic value was assessed using distant recurrence-free interval. Agreement between SSP and NC for PAM50 (five subtypes) was high (85%, Kappa = 0.78) for Subtype (four subtypes) very high (90%, Kappa = 0.84) and for ROR risk category high (84%, Kappa = 0.75, weighted Kappa = 0.90). Prognostic value was assessed as equivalent and clinically relevant. Agreement with histopathology was very high or high for receptor status, while moderate for Ki67 status and poor for Nottingham histological grade. SSP and Prosigna concordance was high for subtype (OSLO-EMIT0 83%, Kappa = 0.73 and ABiM 80%, Kappa = 0.72) and moderate and high for ROR risk category (68 and 84%, Kappa = 0.50 and 0.70, weighted Kappa = 0.70 and 0.78). Pooled concordance for emulated treatment recommendation dichotomized for chemotherapy was high (85%, Kappa = 0.66). Retrospective evaluation suggested that SSP application could change chemotherapy recommendations for up to 17% of postmenopausal ER+/HER2-/N0 patients with balanced escalation and de-escalation. Results suggest that NC and SSP models are interchangeable on a group-level and nearly so on a patient level and that SSP models can be derived to closely match clinical tests.

Predictive Biomarkers of Response to Neoadjuvant Chemotherapy in Breast Cancer: Current and Future Perspectives for Precision Medicine.

Simple SummaryDespite the increased use of neoadjuvant chemotherapy in the early setting of breast cancer, there is a clinical need for predictive markers of response in daily practice. In the era of precision medicine and personalized treatment, new predictive markers that enable the better selection of patients for specific therapies are required. In this review, we describe the current knowledge about the molecular biomarkers used for clinical decision making for patients with breast cancer. We also report how microenvironment-driven intratumoral heterogeneity may influence the validation of biomarkers useful for precision medicine. We provide an overview of promising biomarkers, including pathological markers, genetic signatures, radiological techniques and liquid biopsies, with a great potential to be implemented in routine clinical practice. Finally, we discuss the use of relevant pre-clinical models of breast cancer to integrate microenvironmental specificities in order to identify and validate reliable biomarkers of (non-)response to neoadjuvant chemotherapy.Pathological complete response (pCR) after neoadjuvant chemotherapy in patients with early breast cancer is correlated with better survival. Meanwhile, an expanding arsenal of post-neoadjuvant treatment strategies have proven beneficial in the absence of pCR, leading to an increased use of neoadjuvant systemic therapy in patients with early breast cancer and the search for predictive biomarkers of response. The better prediction of response to neoadjuvant chemotherapy could enable the escalation or de-escalation of neoadjuvant treatment strategies, with the ultimate goal of improving the clinical management of early breast cancer. Clinico-pathological prognostic factors are currently used to estimate the potential benefit of neoadjuvant systemic treatment but are not accurate enough to allow for personalized response prediction. Other factors have recently been proposed but are not yet implementable in daily clinical practice or remain of limited utility due to the intertumoral heterogeneity of breast cancer. In this review, we describe the current knowledge about predictive factors for response to neoadjuvant chemotherapy in breast cancer patients and highlight the future perspectives that could lead to the better prediction of response, focusing on the current biomarkers used for clinical decision making and the different gene signatures that have recently been proposed for patient stratification and the prediction of response to therapies. We also discuss the intratumoral phenotypic heterogeneity in breast cancers as well as the emerging techniques and relevant pre-clinical models that could integrate this biological factor currently limiting the reliable prediction of response to neoadjuvant systemic therapy.

Evolving Role of Risk Tailored Therapy in Early Stage HER2-Positive Breast Cancer: A Canadian Perspective.

The advent of HER2-targeted therapies has led to an important shift in the management of HER2-positive early breast cancer. However, initial treatment approaches apply uniform treatment regimens to all patients, with significant treatment-related and financial toxicities for both the patient and the health care system. Recent data demonstrates that for many patients, the chemotherapy backbone, duration and nature (mono- versus dual-targeted therapy) of the HER2 blockade can be better targeted to an individual patient’s risk of recurrence. We will provide a review of current data supporting risk tailored therapy in early stage HER2-positive breast cancer along with key completed and ongoing Canadian and international risk tailored trials. Neoadjuvant systemic therapy should now be considered for patients with clinical stage 2 disease, with greater use of non-anthracycline based chemotherapy regimens. Patients with residual disease following neoadjuvant therapy should be considered for escalated treatment with adjuvant T-DM1. Patients with stage I disease can often be managed with upfront surgery and evidence-based de-escalated adjuvant chemotherapy regimens. The modest benefit of 12- versus 6 months of adjuvant HER2 therapy and/or dual adjuvant HER2 therapy should be carefully weighed against the toxicities. All patients with HER2-positive breast cancer should be enrolled in ongoing risk tailored treatment trials whenever possible. Increasing data supports risk tailored therapy in early stage HER2-positive breast cancer in place of the routine application of aggressive and toxic systemic therapy regimens to all patients. While much progress has been made towards treatment de-escalation in appropriate patients, more is needed, as we highlight in this review. Indeed, Canadian-led clinical trials are helping to lead these efforts.

Breast Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

The therapeutic options for patients with noninvasive or invasive breast cancer are complex and varied. These NCCN Clinical Practice Guidelines for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of ductal carcinoma in situ and the workup and locoregional management of early stage invasive breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org.

Management of HER2-Positive Early Breast Cancer in Italy: A Maze Presenting Opportunities and Challenges.

The management of human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer (BC) has changed in recent years thanks to the introduction of anti-HER2 agents in clinical practice as standard of care in the neoadjuvant setting. In this scenario, we probed the issue of which HER2-positive BC patients are eligible for neoadjuvant or for adjuvant treatment, since these therapeutic strategies seem to be mutually exclusive in clinical practice according to an Italian drug surveillance system. We reviewed both alternatives to establish which is more suitable, considering the anti-HER2 drugs available in Italy. Randomized clinical trials demonstrated a similar clinical benefit for chemotherapy administered as neoadjuvant therapy or adjuvant therapy. A meta-analysis, including 11,955 patients treated with neoadjuvant therapy, demonstrated an improvement in event-free survival (EFS) and overall survival (OS). Moreover, the recent APHINITY trial, analyzed at 6 years follow-up, demonstrated the superiority of the combination pertuzumab–trastuzumab versus trastuzumab–placebo in previously untreated patients. A greater benefit was found in patients with positive lymph nodes treated in the adjuvant setting. Our analysis underlines the need for a therapeutic decision-making algorithm, which is still unavailable, to support clinicians in identifying patients suitable for neoadjuvant or adjuvant therapy. Further prospective clinical trials should be performed in collaboration with other Italian Breast Cancer Centers to establish the best strategy to be adopted in early HER2+ BC.

Impact of COVID-19 Disease in Early Breast Cancer Management: A Summary of the Current Evidence.

PURPOSEAn expert panel on breast cancer and COVID-19 disease was convened to address the impact of the COVID-19 pandemic for early breast cancer (eBC) management.METHODSTo ensure that the most clinically relevant information was addressed, essential information was drawn from several of the latest national and international guidelines and another technical document. The expert panel met in five virtual closed sessions from November 2020 to May 2021 to consult on the relevant data from evidence-based results. The data gathered were discussed on an online platform.RESULTSThis article reports the expert panel's highlights of these meetings' discussions. In addition, it provides practical recommendations covering topics regarding diagnosis, treatment, and management of patients with eBC in clinical settings routinely encountered by health care professionals amid the COVID-19 pandemic.CONCLUSIONThis article provided guidance on several topics regarding eBC management amid the COVID-19 pandemics to inform safer care practices.

242P Patterns of management of positive sentinel lymph nodes in breast cancer patients after the American College of Surgeons Oncology Group Z0011 trial: A retrospective cohort

The management of axillary lymph nodes in breast cancer patients has changed over the past years. The ACOSOG-Z0011 clinical trial introduced drastic changes to the traditional surgical practice for early breast cancer with positive sentinel lymph nodes (SLNs). This study evaluates how these changes have affected the surgical management of early breast cancer at our institution.

52P RNA sequencing-based single sample predictors of molecular subtype and risk of recurrence for clinical assessment of early-stage breast cancer

Multigene expression assays for molecular subtypes and biomarkers can aid clinical management of early invasive breast cancer. Based on RNA-sequencing we aimed to develop single-sample predictor (SSP) models for conventional clinical markers, molecular intrinsic subtype and risk of recurrence (ROR).

82P Clinical application of a genomic tool for decision support in breast cancer patients in Scotland

There is growing evidence for incorporating genomic assays into the individualised management of early stage luminal HER2-negative breast cancer. TAILORx showed the effectiveness of the Recurrence Score (RS) in this group. RxPONDER evaluated its use in the node-positive setting. Genomic assays should enable accurate assessment of a tumour’s risk of distant recurrence and benefit from chemotherapy. The Oncotype DX Breast RS test has been adopted in Scotland, and has been the subject of a large population based study by the Scottish Consensus Group to assess the uptake of the RS value, and to analyse the effect it has had on clinical practice.

Awareness and practice of breast self-examination (BSE) with its socio-demographic associates

Introduction: Breast cancer is the most common cancer of women worldwide. Early diagnosis of it has a very important role in its management. Breast self-examination (BSE) is a key to the early diagnosis of breast cancer. Materials and Methods: A community-based cross-sectional study was conducted on 300 females of Jaipur city. This study was conducted by a house-to-house survey through a systematic random sampling technique in the field practice area of the Urban Health Training Centre (UHTC) of SMS medical college, Jaipur (Rajasthan), India. A predesigned semi-structured questionnaire containing predesigned questions regarding knowledge and practice of BSE was used to collect data. A Chi-square test was used to find out associations. Results: Only 18% of females were aware of BSE and 5.7% of the females were practicing BSE. Health professionals (31.03%) were the main source of knowledge. Only 50% of females who have heard the name of BSE, knew that it is performed by self. Awareness and practice of BSE both were found to be associated with religion, education, socioeconomic status, and occupation and there was no association with age and marital status. Females with higher education and socioeconomic status were more aware of BSE. The most common (94.69%) reason for not practicing BSE was the lack of awareness of steps followed by ‘find it unnecessary’. Conclusion: As knowledge and practice of BSE were observed very poor and considering the important role that can be played by BSE in the early diagnosis and management of breast cancer, there is an urgent need to implement and reinforce BSE in the existing cancer awareness and screening programs. IEC activities regarding BSE also motivated proper knowledge of BSE.

Management of early stage HER2 positive breast cancer and increased implementation of axillary imaging to improve identification of nodal metastasis.

Given the significant benefit of targeted therapies for HER2+ breast cancer patients in both the neoadjuvant and adjuvant settings, it is critical to identify all eligible patients for these treatments. We sought to investigate cT1cN0 HER2+ patients to determine the rate of postsurgical nodal positivity, and to identify presurgical factors associated with nodal positivity. We hypothesize there is a subset of underdiagnosed HER2+ patients who would benefit from preoperative axillary imaging and inclusion in neoadjuvant chemotherapy regimens. We performed a 10-year retrospective analysis of T1 HER2+ breast cancer patients. Clinicopathologic characteristics were evaluated based on surgical nodal data. We identified 38 patients with cT1cN0 HER2+ cancer. Of this cohort, 24% had positive lymph nodes on final pathology. High tumor grade (p = 0.035) on core needle biopsy and the presence of lymphovascular invasion (p = 0.0036) were associated with an increased likelihood of lymph node positivity. The majority (66%) of lymph node positive patients were clinically T1c. We identified a 24% nodal positivity rate in clinically node negative T1 HER2+ breast cancer patients. In particular, HER2+ patients with high-grade T1c cancers should undergo preoperative diagnostic axillary imaging to expand potential benefit from targeted therapies.

Neoadjuvant Pertuzumab Plus Trastuzumab in Combination with Docetaxel and Carboplatin in Patients with HER2-Positive Breast Cancer: Real-World Data from the National Institute of Oncology in Poland.

Simple SummaryNeoadjuvant chemotherapy in HER2-positive breast cancer has become the standard of care. Systemic treatment allows, in many cases, a reduction in the scope of surgical treatment. The aim of our retrospective study was to confirm the efficacy and safety of neoadjuvant chemotherapy in the TCbH-P program. All study patients received six courses of chemotherapy. All patients achieved a reduction in breast tumour size. There were no cardiac complications in any of the patients that prevented the continuation of treatment. A complete pathological response was achieved in 52.9% of patients. No pCR was achieved in any patient over 60 years of age with luminal B HER2-positive cancer, which questions the use of the TCbH-P regimen in this group of patients.Neoadjuvant systemic therapy has now become the standard in early breast cancer management. Chemotherapy in combination with trastuzumab +/− pertuzumab targeted therapy can improve the rates of pathologic complete response (pCR) in patients with HER2-positive breast cancer. Achieving a pCR is considered a good prognostic factor, in particular, in patients with more aggressive breast cancer subtypes such as TNBC or HER2-positive cancers. Furthermore, most studies demonstrate that chemotherapy in combination with trastuzumab and pertuzumab is well tolerated. The retrospective analysis presented here concentrates on neoadjuvant therapy with the TCbH-P regimen, with a particular emphasis on patients over 60 years of age. We analysed the factors affecting the achievement of pCR and present the adverse effects of the applied therapies, opening discussion about optimizing the therapy of older patients with HER-2 positive breast cancer.

Reliability of Oncoplastic Breast Conserving Surgery for Management of Early Breast Cancer in Yemeni Patients

Background: Oncoplastic breast conserving surgery is limited in treatment of Yemeni breast cancer. The aim of this study is to evaluate the reliability and safety of oncoplastic breast surgery in Yemeni patients with early breast cancer. Material &amp; Methods: Patients with early breast cancer who underwent oncoplastic breast conserving surgery from July 2014 to July 2020 were included in this retrospective study. Data on the patient’s demographic, tumor characteristics, the type of oncoplastic technique performed, surgical margin involved, re-excision rate, complications, satisfaction, follow up and local recurrence rate were included to evaluate the results. Results: A total of 50 breast cancer patients underwent oncoplastic surgery by using different techniques. Volume displacement technique was the commonest technique used in 92% of the patients (local glandular flap in 64%, reduction mammoplasty in 22%, Grissoti flap in 4% and bat-wing in 2%) While the volume replacement (Latissmus dorsi flap) technique was used in 8 % of the patients with small breasts. 70% of the patients were less than 40 years old. The mean tumor size was 3.4cm. Most of the tumors (84%) was invasive ductal carcinoma. The overall postoperative complication was 14% [wound infection (4%), wound dehiscence (8%) and fat necrosis (2%)]. Re excision rate was 12% and complete mastectomy was performed for 2 patients. Patient satisfaction was 96%. Local recurrence rate was 4% with mean follow up of 23.1 (SD:16) months.Conclusion: The oncoplastic breast conserving surgery is reliable and safe with good oncological and aesthetic outcomes for treatment of early breast cancer in Yemeni patients.

Assessment of Volume Displacement as an Oncoplastic Technique in Management of Early Breast Cancer

Assessment of Volume Displacement as an Oncoplastic Technique in Management of Early Breast Cancer

Impact of Quilting Sutures on Surgical Outcomes After Mastectomy: A Systematic Review and Meta-Analysis.

Seroma after mastectomy and/or axillary lymph node dissection (ALND) is among the most common issue surgeons have to face in the early postoperative management of breast cancer. Using quilting sutures (QS) to aid in tissue approximation and decrease dead space is proposed as a simple technique to reduce seroma rate. We aimed to perform a systematic review, and analyse, in a meta-analytical model, the role of QS in improving wound outcomes and decrease volume, duration of drainage, and length of stay in hospital. The study was registered with PROSPERO. A systematic search of the PubMed, EMBASE, and SCOPUS databases was performed for all comparative studies examining surgical outcomes in patients who underwent QS versus conventional closure (CC) after mastectomy ± ALND. Twenty-one studies with a total of 3473 patients (1736 in the study group and 1737 in the control group) were included based on the selection criteria. The study group showed significantly lower rates of seroma (p<0.00001), total volume of drainage (p<0.0001), days to drain removal (p<0.00001), and length of stay (p<0.00001) compared with the control group, while wound complication rates (surgical site infection, flap necrosis, hematoma, skin dimpling) were comparable between the two groups. QS are a reliable intraoperative technique that decrease seroma formation, volume of postoperative drainage, duration of drainage and length of hospital stay, and should be considered in mastectomies with or without ALND.

Receptor Status after Neoadjuvant Therapy of Breast Cancer: Significance and Implications.

Neoadjuvant chemotherapy (NACT) is now established in routine management of early breast cancer. Alterations in oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) following NACT are reported, with wide variation in results across series. In larger series, changes in ER status are identified in 5-23%, whilst changes in PR status are more frequent (14.5-67%). HER2 status changes less frequently with loss being more common than gain, and higher rates of change with immunohistochemistry are observed compared to in situ hybridization and following HER2-targeted therapy compared with chemotherapy alone. Triple negative is the most stable molecular subtype with combined ER, and HER2-positive cancers show the highest rate of change. Neoadjuvant endocrine therapy is used less commonly than NACT, and whilst loss of ER is rare, changes in PR status can occur in up to 40% of cases. There is relatively little published data on the impact of change in receptor status on survival outcomes. In patients whose tumours become ER or HER2 positive post-NACT, endocrine or anti-HER2 therapy can be initiated, although evidence from clinical trials is lacking. Most guidelines do not currently recommend routine retesting; however it should be considered in some circumstances.

Efficacy of the Management of Node Negative Early Stage Breast Cancer Using 1% Methylene Blue in Sentinel Lymph Node Biopsy:prospective study, kasrAlaini University Hospital

Background:Accurate staging and proper management of axillary lymph nodes are important for the treatment of breast cancer. Sentinel lymph node biopsy (SLNB) provides accurate assessment of nodal status.Aimof work:Evaluation the safety, the accuracy and the cost of the application of SLNB using methylene blue 1% (MB 1%) in cases of node negative early stage breast cancer.Patients and methods:This study was conducted at Kasr Al-Ainy university Hospitals, Faculty of Medicine, Cairo University. Fifty-two female patients with node negative early stage breast cancer who agreed on undergoing breast conservative surgery( BCS), SLNB using 1% methylene blue and frozen section examination then managed according to ACOSOG Z0011 criteria .Results:Identification in 50 surgical specimens (identification rate 96.15%). By evaluating frozen section examination of the lymph nodes in relation to paraffin section examination we found that the sensitivity of the frozen section examination was 100% and specificity was 97.5% with positive predictive value 90.9%, negative predictive value 100% and overall accuracy was 98%.Conclusion:One % MB dye is very effective as a single agent in SLNB in node negative early stage breast cancer with very high identification rate compared to patent blue and radiocolloids. Implementation of ACOSOG Z0011 criteria proved its validity throughout our study as average 12 months follow up showed no locoregional recurrence