Systemic Treatment Of Breast Cancer Research Articles

Abstract PO5-18-10: Omission of SLNB in triple-negative and HER2-positive breast cancer patients with radiologic and pathologic complete response in the breast after NAST: a single-arm, prospective surgical trial (EUBREAST-01 trial, GBG 104)

Abstract Background: Currently, axillary surgery for breast cancer is considered a staging procedure that does not seem to influence breast cancer mortality since the risk of developing metastasis depends mainly on the biological behavior of the primary (seed-and-soil model). Based on this, postsurgical therapy should be considered based on biological tumor characteristics. Retrospective data of cancer registry trials showed a strong correlation between breast pathologic complete response (pCR) and nodal pCR depending on intrinsic subtypes. Improvements in systemic treatments for breast cancer have increased the rates of pCR in patients receiving neoadjuvant systemic therapy (NAST), offering the opportunity to decrease, and perhaps eliminate, surgery in patients who have a pCR. Trial design: The EUBREAST network designed a clinical trial (NCT04101851) in which only patients with the highest likelihood of having a pCR after NAST (triple-negative or HER2-positive breast cancer) will be included, and type of surgery will be defined according to the response to NAST rather than on the classical T and N status at presentation. In the ongoing trial, axillary surgery will be eliminated (no axillary sentinel lymph node biopsy [SLNB]) for initially clinical node-negative (cN0) patients with radiologic complete remission (rCR) and a breast pCR (ypT0/ypTis) as determined in the lumpectomy specimen. The trial design is a multicenter single-arm study with a limited number of patients (N=440 as the screening population with an expected 80% pCR-rate) which might give practice-changing results in a short period, sparing the time and the costs of a randomized comparison. Patients will be recruited in European countries (Austria, Germany, Italy, and Spain) over 48 months. Inclusion criteria: -Written informed consent -Histologically confirmed unilateral primary invasive carcinoma of the breast (core biopsy). Multifocal or multicentric tumors are allowed if breast-conserving surgery (BCS) is planned. -Age at diagnosis at least 18 years -imaging techniques with estimated tumor stage between cT1-T3 before NAST -triple-negative (TNBC) or HER2-positive invasive breast cancer -TNBC is defined by: ER-negative (< 10% positive cells in IHC) and PgR-negative (< 10% positive cells in IHC), HER2-negative -clinically and sonographically tumor-free axilla before core biopsy (cN0/iN0) -in cases with cN0 and iN+, a negative core biopsy or fine-needle aspiration biopsy of the sonographically suspected lymph node is required -no evidence for distant metastasis (M0) -standard NAST with rCR -planned BCS with postoperative external whole-breast irradiation (conventional fractionation or hypofractionation) Primary objective: 3-year rate of axillary recurrence-free survival (ARFS) after BCS Statistics: The calculated total case number for per-protocol analysis is N=350, and the expected total number of screened patients is N=440. The assumption for acceptable 3-year ARFS ≥98.5% in the experimental arm is based on previous study findings. Timelines: -First patient in: January 2021 -Last patient in: December 2024 -Primary outcome analysis: Q1/2027 Current accrual: In June 2023, 255 patients were recruited; the majority of them in Germany. Contact: Prof. Dr. Toralf Reimer (eubreast-01@kliniksued-rostock.de), study chair Dr. Oreste D. Gentilini (gentilini.oreste@hsr.it), study co-chair Funding by Else Kroener-Fresenius Foundation, German Society of Senology, University of Rostock (Germany), and San Raffaele Hospital (Milan, Italy). Citation Format: Toralf Reimer, Bernd Gerber, Thorsten Kuehn, Nikola Bangemann, Anke Kleine-Tebbe, Andrea Stefek, Ulrike Doerste, Carolin Hammerle, Oliver Hoffmann, Alexander Hein, Isabel Rubio, Florentia Peintinger, Keyur Mehta, Sibylle Loibl, Edoardo Botteri, Oreste Gentilini. Omission of SLNB in triple-negative and HER2-positive breast cancer patients with radiologic and pathologic complete response in the breast after NAST: a single-arm, prospective surgical trial (EUBREAST-01 trial, GBG 104) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-18-10.

Protocol for the development of a core outcome set and reporting guidelines for locoregional treatment in neoadjuvant systemic breast cancer treatment trials: the PRECEDENT project

IntroductionNeoadjuvant systemic anticancer therapy (neoSACT) is increasingly used in the treatment of early breast cancer. Response to therapy is prognostic and allows locoregional and adjuvant systemic treatments to be tailored...

Information and communication priorities of patients and healthcare professionals in shared decision making regarding adjuvant systemic breast cancer treatment: A survey study

PurposeTo assess information and communication priorities of patients and healthcare professionals in Shared Decision Making about adjuvant systemic treatment of primary breast cancer and identify key decision-relevant information accordingly. MethodsPatients (N = 122) and professionals working with breast cancer patients (N = 118), of whom 38 were nurse practitioners and 32 nurses, were recruited using convenience sampling, and surveyed about information/communication aspects key to decision-making, using ranking assignments. We further posed a simple open question, questions about receiving population-based statistics versus personalized statistics concerning treatment outcomes, and their attitude and experience concerning Shared Decision Making. Data were analyzed using descriptive analysis and a qualitative analysis. ResultsBoth patients and professionals prioritized information about treatment outcomes (i.e., survival, recurrence) as key decision-relevant information for patients. Patients prioritized information about relatively severe treatment side-effects and late effects (e.g., blood clot, stroke), whilst professionals prioritized information about effects that occur relatively often (e.g., hair loss, fatigue). Patients specifically wanted to know if the benefit of treatment is worth the negative impact. Both groups prioritized personalized statistics over population-based statistics. ConclusionsSome differences between patients and professionals were found in information and communication priorities, specifically related to the different side-effects. It seems worthwhile to precisely address these side-effects in Shared Decision Making concerning adjuvant systemic treatment. Furthermore, it seems important to deliberate together on the question if expected benefit of treatment is worth the potential negative impact for the individual patient.

HER2-Positive Early Breast Cancer: Time for Ultimate De-Escalation?

De-escalation is currently taking place in both the surgical and systemic treatment of breast cancer. The introduction of trastuzumab, the first monoclonal antibody against the HER2 receptor, over 20 years ago was a milestone in the treatment of HER2-positive breast cancer and marked the beginning of a new era in targeted tumor therapy. In the sense of de-escalation, omitting non-targeted cytotoxic chemotherapy altogether is often hailed as the ultimate goal of oncological research. Especially in cases of small, node-negative, HER2-positive early breast cancer, it remains a challenge for clinicians to establish the safest and most efficient treatment plan while considering the significant potential for toxic side effects associated with chemotherapy and HER2-targeted therapy, and the generally excellent prognosis. In this context, several ongoing studies are currently assessing chemotherapy-free regimens as part of strategies aimed at de-escalating therapy in the field of HER2-positive early breast cancer. Despite the promising early results of these studies, the combination of anti-HER2 treatment with a chemotherapy backbone remains the standard of care.

Metformin as an adjuvant option for systemic treatment of breast cancer

The modification of the used and development of new treatment regimens significantly improved the overall, recurrence-free survival and quality of life of patients with malignant oncological diseases. Recently, drugs used in non-oncological pathology have been introduced into cancer treatment regimens. This phenomenon is associated with a better understanding of the biology of tumor cells and the mutations that can change this biology. Metformin is actively researched in terms of the treatment of various oncological diseases. For the most part, the modification of the neoadjuvant treatment regimen for local or locally advanced stages of breast cancer results in a less traumatic variant of surgical procedure, thereby increasing recurrence-free survival. The aim is to systematize the data on the possibilities of the antitumor metformin usage for neoadjuvant treatment of breast cancer and to study the results of clinical and morphological effectiveness of the treatment by reviewing the literature. A search of PubMed from February 2023 showed 258 results on the antitumor effects of metformin, of which only 159 were published in the last 5 years. On this subject only four clinical studies were carried out, and only one of them pertained to the implementation of metformin in the systemic treatment of breast cancer. For this review, 55 sources of general and specialized information on anticancer effects of metformin were analyzed. It should be noted that approximately 60% of the study results were published more than 5 years ago and primarily focused on the biological, not clinical aspects of metformin usage. Only one study regarding the implementation of metformin for systemic treatment of breast cancer was carried out by Ukrainian scientists. Currently, there are 2 main hypotheses regarding the antitumor effect of metformin. First one is driven by its impact on the metabolic function of cells and energy deficit. Second - the method of regulating the proliferation of tumor cells involves the PIK3 branch of the regulatory cascade of biological reactions in cancer cells. In addition, metformin reduces the development of resistance in breast cancer cells, thus allowing active chemotherapy agents to act in synergism. However, further studies on the effect of metformin used alone or in combination with standard chemotherapy regimens require a more adequate definition of proto-oncogenic mutations and somatic mutation load. However, it should be considered that more aggressive therapy of oncological diseases can be a nosocomial selector of more aggressive clones of the pool of tumor cells. The main questions are whether metformin can be a targeted drug for the treatment of tumor, whether it is appropriate to use it at the time when the manifestation of evolution disturbances of tumor cell is minimal and homogeneity is maximal.

Invasive lobular carcinoma of the breast with colonic metastasis: a case series of three patients

BackgroundAlthough metastatic spread of breast cancer to the gastrointestinal tract is very rare, it is more likely to occur in invasive lobular carcinoma (ILC) than in ductal carcinoma. Colonic metastasis is particularly rare, and the treatment strategies for these cases are not clearly defined. Herein, we report three cases of ILC with various abdominal symptoms associated with colonic metastasis.Case presentationCase 1 A 70-year-old female patient with vomiting and melena was referred to our hospital. Endoscopic examination revealed a Dieulafoy ulcer in the rectum and an elevated lesion in the descending colon. She also had two breast nodules, and was diagnosed as ILC with colonic metastasis. Considering her general condition, the best supportive care (BSC) was offered. The patient died 4 months after confirmation of the diagnosis. Case 2 An 80-year-old female patient presented with diarrhea and vomiting. She was diagnosed with ILC with colonic metastasis, and a coloscopy revealed stenosis of the transverse colon with a metastatic lesion. Ileosigmoid bypass surgery was performed for intestinal obstruction, and systemic treatment for breast cancer was initiated. The patient developed peritoneal carcinomatosis and died 1 year and 2 months after surgery. Case 3 A 56-year-old female patient underwent left total mastectomy for ILC, and laparoscopic transverse colectomy was conducted for a colonic lesion 9 years and 2 months after. The diagnosis as colonic metastasis was not confirmed at that time. Two years and 2 months later, torose lesions were detected in the hepatic flexural and descending colon, and histopathological findings indicated that all colon tumors, including the previously resected tumor, were metastatic spread of ILC. Systemic treatment was continued, but the transverse colonic lesion penetrated the abdominal wall, and an abscess formed 2 years and 11 months after the resection. The fistula improved by continuous suction drainage following ileostomy but recurred, and the patient died 3 years and 8 months after colectomy.ConclusionsColonic metastases from breast cancer can trigger various abdominal symptoms, and the prognosis in these cases is generally poor. In selected cases, surgical treatment for abdominal symptoms and subsequent systemic therapy can contribute to a prolonged prognosis.

The Japanese Breast Cancer Society Clinical Practice Guidelines for systemic treatment of breast cancer, 2022 edition

The Japanese Breast Cancer Society (JBCS) Clinical Practice Guidelines for systemic treatment of breast cancer were updated to the 2022 edition through a process started in 2018. The updated guidelines consist of 12 background questions (BQs), 33 clinical questions (CQs), and 20 future research questions (FRQs). Multiple outcomes including efficacy and safety were selected in each CQ, and then quantitative and qualitative systematic reviews were conducted to determine the strength of evidence and strength of recommendation, which was finally determined through a voting process among designated committee members. Here, we describe eight selected CQs as important updates from the previous guidelines, including novel practice-changing updates, and recommendations based on evidence that has emerged specifically from Japanese clinical trials.

Can multi-modal radiomics using pretreatment ultrasound and tomosynthesis predict response to neoadjuvant systemic treatment in breast cancer?

ObjectivesResponse assessment to neoadjuvant systemic treatment (NAST) to guide individualized treatment in breast cancer is a clinical research priority. We aimed to develop an intelligent algorithm using multi-modal pretreatment ultrasound and tomosynthesis radiomics features in addition to clinical variables to predict pathologic complete response (pCR) prior to the initiation of therapy.MethodsWe used retrospective data on patients who underwent ultrasound and tomosynthesis before starting NAST. We developed a support vector machine algorithm using pretreatment ultrasound and tomosynthesis radiomics features in addition to patient and tumor variables to predict pCR status (ypT0 and ypN0). Findings were compared to the histopathologic evaluation of the surgical specimen. The main outcome measures were area under the curve (AUC) and false-negative rate (FNR).ResultsWe included 720 patients, 504 in the development set and 216 in the validation set. Median age was 51.6 years and 33.6% (242 of 720) achieved pCR. The addition of radiomics features significantly improved the performance of the algorithm (AUC 0.72 to 0.81; p = 0.007). The FNR of the multi-modal radiomics and clinical algorithm was 6.7% (10 of 150 with missed residual cancer). Surface/volume ratio at tomosynthesis and peritumoral entropy characteristics at ultrasound were the most relevant radiomics. Hormonal receptors and HER-2 status were the most important clinical predictors.ConclusionA multi-modal machine learning algorithm with pretreatment clinical, ultrasound, and tomosynthesis radiomics features may aid in predicting residual cancer after NAST. Pending prospective validation, this may facilitate individually tailored NAST regimens.Clinical relevance statementMulti-modal radiomics using pretreatment ultrasound and tomosynthesis showed significant improvement in assessing response to NAST compared to an algorithm using clinical variables only. Further prospective validation of our findings seems warranted to enable individualized predictions of NAST outcomes.Key Points• We proposed a multi-modal machine learning algorithm with pretreatment clinical, ultrasound, and tomosynthesis radiomics features to predict response to neoadjuvant breast cancer treatment.• Compared with the clinical algorithm, the AUC of this integrative algorithm is significantly higher.• Used prior to the initiative of therapy, our algorithm can identify patients who will experience pathologic complete response following neoadjuvant therapy with a high negative predictive value.

Reporting of older subgroups in registration breast cancer trials 2012-2021.

Adequate reporting of data specific to older populations enrolled to breast cancer trials is critical, given the high incidence of the disease among this demographic. This study aimed to examine the completeness of reporting of older subgroups among patients recruited to registration clinical trials investigating systemic treatments for breast cancer. Clinical trials leading to a US food and drug administration (FDA) approval in breast cancer between 2012 and 2021 were included. Primary study reports and and all available secondary publications were systematically and objectively assessed with regard to the availability of data regarding efficacy, baseline characteristics, safety, and health-related quality of life (HRQOL) outcomes among older subgroups. 27 trials and 216 publications were assessed. 20.3% of patients were aged ≥65. 70.0% of patients had an eastern cooperative oncology group (ECOG) performance status of 0. Although complete reporting of primary endpoints was adequate (72.7%), most protocol-defined primary endpoints were surrogate endpoints (84.8%). Overall survival data among older populations was unavailable in 50.0% of studies. Reporting was poor for secondary efficacy endpoints (81.8% unreported), baseline characteristics (70.4% unreported), toxicity (55.6% unreported), and health-related quality of life outcomes (87.5% unreported). The findings underline significant deficits in the reporting of age-specific data in breast cancer registration trials. The underreporting of key efficacy, safety, and HRQOL outcomes highlights the need for mandatory reporting standards and a dedicated emphasis on older populations' priorities and needs in the reporting of registration clinical trials.

Coencapsulation of Gemcitabine and Thymoquinone in Citrem-Phosphatidylcholine Hexosome Nanocarriers Improves In Vitro Cellular Uptake in Breast Cancer Cells.

Lyotropic liquid crystalline nanoassemblies (LLCNs) are internally self-assembled (ISA)-somes formed by amphiphilic molecules in a mixture comprising a lipid, stabilizer, and/or surfactant and aqueous media/dispersant. LLCNs are unique nanoassemblies with versatile applications in a wide range of biomedical functions. However, they comprise a nanosystem that is yet to be fully explored for targeted systemic treatment of breast cancer. In this study, LLCNs proposed for gemcitabine and thymoquinone (Gem-TQ) co-delivery were prepared from soy phosphatidylcholine (SPC), phytantriol (PHYT), or glycerol monostearate (MYVR) in optimized ratios containing a component of citric and fatty acid ester-based emulsifier (Grinsted citrem) or a triblock copolymer, Pluronic F127 (F127). Hydrodynamic particle sizes determined were below 400 nm (ranged between 96 and 365 nm), and the series of nanoformulations displayed negative surface charge. Nonlamellar phases identified by small-angle X-ray scattering (SAXS) profiles comprise the hexagonal, cubic, and micellar phases. In addition, high entrapment efficiency that accounted for 98.3 ± 0.1% of Gem and 99.5 ± 0.1% of TQ encapsulated was demonstrated by the coloaded nanocarrier system, SPC/citrem/Gem-TQ hexosomes. Low cytotoxicity of SPC-citrem hexosomes was demonstrated in MCF10A cells consistent with hemo- and biocompatibility observed in zebrafish (Danio rerio) embryos for up to 96 h postfertilization (hpf). SPC/citrem/Gem-TQ hexosomes demonstrated IC50 of 24.7 ± 4.2 μM in MCF7 breast cancer cells following a 24 h treatment period with the moderately synergistic interaction between Gem and TQ retained (CI = 0.84). Taken together, biocompatible SPC/citrem/Gem-TQ hexosomes can be further developed as a multifunctional therapeutic nanodelivery approach, plausible for targeting breast cancer cells by incorporation of targeting ligands.

Sexual health in long-term breast cancer survivors: a comparison with female population controls from the HUNT study

PurposeSexual health is an important aspect of quality of life. Knowledge concerning sexual health in long-term breast cancer survivors (BCSs) is limited. This study compared sexual health in BCSs 8 years after diagnosis with similarly aged controls and examined the impact of menopausal status at diagnosis and systemic breast cancer treatments on sexual health.MethodsWomen aged 20–65 years when diagnosed with stage I–III breast cancer in 2011–2012 were identified by the Cancer Registry of Norway (n = 2803) and invited to participate in a nationwide survey. Controls were women from the Trøndelag Health Study (HUNT4). Sexual functioning and sexual enjoyment were measured by the EORTC QLQ-BR23 subscales scored from 0 to 100, and sexual discomfort by the Sexual Activity Questionnaire scored from 0 to 6. Linear regression analyses with adjustments for sociodemographic and health-related variables were performed to compare groups. Differences of ≥ 10% of range score were considered clinically significant.ResultsThe study samples consisted of 1241 BCSs and 17,751 controls. Sexual enjoyment was poorer (B − 13.1, 95%CI − 15.0, − 11.2) and discomfort higher (B 0.9, 95%CI 0.8, 1.0) among BCSs compared to controls, and larger differences were evident between premenopausal BCSs and controls (B − 17.3, 95%CI − 19.6, − 14.9 and B 1.2, 95%CI 1.0, 1.3, respectively). BCSs treated with both endocrine- and chemotherapy had lower sexual functioning (B − 11.9, 95%CI − 13.8, − 10.1), poorer sexual enjoyment (B − 18.1, 95%CI − 20.7, − 15.5), and more sexual discomfort (B 1.4, 95% 1.3, 1.6) than controls.ConclusionSexual health impairments are more common in BCSs 8 years after diagnosis compared to similar aged population controls. During follow-up, attention to such impairments, especially among women diagnosed at premenopausal age and treated with heavy systemic treatment, is warranted.

EVALUATION OF THE EFFECTIVENESS OF NEOADJUVANT CHEMOTHERAPY IN BREAST CANCER

Relevance: Breast cancer is the most common cancer among women. Modern treatment of locally advanced breast cancer requires a multidisciplinary approach, including local treatment: surgical and radiotherapy, systemic treatment, and a wide range of medications. The importance of systemic therapy is to improve relapse-free survival based on the control of micrometastases with the potential to spread throughout the body.
 Systemic therapy for operable breast cancer includes adjuvant therapy and neoadjuvant therapy. Hormone therapy, chemotherapy, and targeted therapy represent systemic therapy, which can be prescribed individually or in combination.
 For the most effective breast cancer treatment, tumors are classified into subtypes depending on the expression of biological markers. The presence of expression of the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and the rate at which tumor cells divide are determined by determining the Ki67.
 It is known that neoadjuvant chemotherapy (NCT) has clinical significance in locally advanced and inoperable breast cancer. NCT increases the frequency of organ-preserving operations and the overall survival rate when a complete pathomorphological regression of the tumor (pCR) is achieved.
 The study aimed to conduct a literature review of previously published publications on the effectiveness and expediency of neoadjuvant chemotherapy for breast cancer.
 Methods: The search and analysis of scientific publications were carried out in the databases Web of Science, Pubmed, and Scopus for ten years, from 2013 to 2023. According to the search, about 3000 articles were found, and 39 sources were left during the selection according to the inclusion and exclusion criteria
 Results: Efficiency of NСT depending on different immunophenotypes in breast cancer patients was established. Tumor response was assessed according to RECIST criteria. A complete pathological response was observed more often in more aggressive subtypes of breast cancer – Her2-positive and triple-negative cancer. The relationship between pCR and long-term outcomes – OS and DFS have also been established.
 Conclusion: Neoadjuvant chemotherapy is a systemic treatment of breast cancer, the main purpose of which is to reduce the size of the tumor for the possibility of performing organ-preserving surgery, as well as to increase the overall and relapse-free survival rates. NCT allows for evaluating the effectiveness of therapy in vivo and using alternative treatment regimens without tu-mor response to the therapy.

EVALUATION OF THE EFFECTIVENESS OF NEOADJUVANT CHEMOTHERAPY IN BREAST CANCER

Relevance: Breast cancer is the most common cancer among women. Modern treatment of locally advanced breast cancer requires a multidisciplinary approach, including local treatment: surgical and radiotherapy, systemic treatment, and a wide range of medications. The importance of systemic therapy is to improve relapse-free survival based on the control of micrometastases with the potential to spread throughout the body.
 Systemic therapy for operable breast cancer includes adjuvant therapy and neoadjuvant therapy. Hormone therapy, chemotherapy, and targeted therapy represent systemic therapy, which can be prescribed individually or in combination.
 For the most effective breast cancer treatment, tumors are classified into subtypes depending on the expression of biological markers. The presence of expression of the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and the rate at which tumor cells divide are determined by determining the Ki67.
 It is known that neoadjuvant chemotherapy (NCT) has clinical significance in locally advanced and inoperable breast cancer. NCT increases the frequency of organ-preserving operations and the overall survival rate when a complete pathomorphological regression of the tumor (pCR) is achieved.
 The study aimed to conduct a literature review of previously published publications on the effectiveness and expediency of neoadjuvant chemotherapy for breast cancer.
 Methods: The search and analysis of scientific publications were carried out in the databases Web of Science, Pubmed, and Scopus for ten years, from 2013 to 2023. According to the search, about 3000 articles were found, and 39 sources were left during the selection according to the inclusion and exclusion criteria
 Results: Efficiency of NСT depending on different immunophenotypes in breast cancer patients was established. Tumor response was assessed according to RECIST criteria. A complete pathological response was observed more often in more aggressive subtypes of breast cancer – Her2-positive and triple-negative cancer. The relationship between pCR and long-term outcomes – OS and DFS have also been established.
 Conclusion: Neoadjuvant chemotherapy is a systemic treatment of breast cancer, the main purpose of which is to reduce the size of the tumor for the possibility of performing organ-preserving surgery, as well as to increase the overall and relapse-free survival rates. NCT allows for evaluating the effectiveness of therapy in vivo and using alternative treatment regimens without tu-mor response to the therapy.

Omitting Sentinel Lymph Node Biopsy after Neoadjuvant Systemic Therapy for Clinically Node Negative HER2 Positive and Triple Negative Breast Cancer: A Pooled Analysis.

Recent advances in systemic treatment for breast cancer have been underpinned by recognising and exploiting subtype-specific vulnerabilities to achieve higher rates of pathologic complete response (pCR) after neo-adjuvant systemic therapy (NAST). This down-staging of disease has permitted safe surgical de-escalation in patients who respond well. Triple-negative (TNBC) or HER2-positive breast cancer is most likely to achieve complete radiological response (rCR) and pCR after NAST. Hence, for selected patients, particularly those who are clinically node-negative (cN0) at diagnosis, the probability of disease in the sentinel node after NAST could be low enough to justify omitting axillary surgery. The aim of this pooled analysis was to determine the rate of sentinel node positivity (ypN+) in patients with TNBC or HER2-positive breast cancer who were initially cN0, achieving rCR and/or pCR in the breast after NAST. MedLine was searched using appropriate search terms. Five studies (N = 3834) were included in the pooled analysis, yielding a pooled ypN+ rate of 2.16% (95% CI: 1.70-2.63). This is significantly lower than the acceptable false negative rate of sentinel lymph node biopsy (SLNB) and supports consideration of omission of SLNB in this subset of patients.

Nonlinear, Multicomponent Physical Exercise with Heart Rate Variability-Guided Prescription in Women with Breast Cancer during Treatment: Feasibility and Preliminary Results (ATOPE Study).

The purpose of this study was to examine the feasibility, safety, adherence, and preliminary efficacy of the ATOPE program during radiotherapy (RT) or chemotherapy (CT) for women with breast cancer. This single-blind, pretest-posttest feasibility study included 38 women with breast cancer at the beginning of their treatment. The ATOPE program consisted of 12 to 18 sessions of a multimodal physical exercise program, prescribed based on daily heart rate variability (HRV) and clinimetric assessments using the ATOPE+ mHealth system. Overall health was assessed with quality of life, autonomous balance, and body composition, whereas health-related fitness (HRF) was measured through functional capacity, physical activity levels, and upper and lower limb strength. The rates of recruitment, retention, and adherence were 52.35%, 73.68%, and 84.37%, respectively, and the satisfaction rating was 9.2 out of a possible 10 points. The perceived health status change score was 3.83 points, scored on a - 5 to 5 point scale. No adverse effects were found. Compliance results showed that the ATOPE+ mHealth system was used on 73.38% of the days, and the Fitbit bracelet (Google, Mountain View, CA, USA) was used on 84.91% of the days. Women stayed physically active 55% of days. Regarding preliminary results, for overall health, the percentage of body fat in the RT group decreased by 1.93%, whereas it increased by 5.03% in the CT group. Lower limb strength increased in the RT group, specifically knee extensor isometric strength (6.07%), isokinetic knee flexors 180°/s (1.53%) and isokinetic knee extensors 300°/s (4.53%), in contrast with the reductions found in the CT group (11.07%, 18.67%, and 14.89%, respectively). The ATOPE program, through nonlinear prescription based on daily monitoring with the ATOPE+ mHealth system, is feasible and safe for application during breast cancer treatment. The results suggest that overall health can be maintained or even improved regarding most variables. This study focused on the feasibility, safety, and completion of a physical therapist-led program at early diagnosis for adults with breast cancer. The multimodal, supervised, tailored, nonlinear physical exercise program is feasible and safe, showed a good completion rate, and was able to prevent the quality-of-life deficits that are often triggered by systemic breast cancer treatment. This study highlights the importance of daily morning assessments using the ATOPE+ mHealth system in patients with breast cancer to prescribe nonlinear physical exercise.

Role of Molecular Targeted Therapeutic Drugs in Treatment of Breast Cancer: A Review Article.

Breast cancer is a multifactor, multistage, and heterogeneous disease. Systemic treatment of breast cancer has changed significantly over the last decade. With a better knowledge of the pathogenesis, researchers and scientists have discovered numerous signaling pathways and synonymous therapeutic targets in breast cancer. Because of the molecular nature of breast cancer, which makes it difficult to understand, previous attempts to treat or prevent it have failed. However, recent decades have provided effective therapeutic targets for treatment. In this review, literature or information on various targeted therapy for breast cancer is discussed. English language articles were explored in numerous directory or databases like PubMed, Web of Sciences, Google Scholar, ScienceDirect, and Scopus. The important keywords used for searching databases are "Breast cancer," "Targeted therapy in breast cancer," "Therapeutic drugs in breast cancer," and "Molecular targets in breast cancer."

Impact of Evaluation of Tumour Grade by Core Needle Biopsy on Clinical Risk Assessment and Patient Selection for Adjuvant Systemic Treatment in Breast Cancer

Introduction: Breast cancer is one of the most common cancers affecting women worldwide. The prognosis and treatment of breast cancer depend largely on various prognostic factors, including tumour grade, hormone receptor status, and HER2/neu overexpression. Objectives: The main objective of the study is to find the impact of evaluation of tumour grade by core needle biopsy on clinical risk assessment and patient selection for adjuvant systemic treatment in breast cancer Material and Methods: This retrospective cohort study was conducted in Services Hospital, Lahore during January 2020 to January 2021. The study participants were women with breast cancer who underwent core needle biopsy for tumour grade evaluation at a single institution during the study period. Results: Of the 70 patients included in the study, the mean age was 58 years (range, 32-85 years), and the majority were postmenopausal (60%). Most patients had invasive ductal carcinoma (IDC) (85%), and the remainder had invasive lobular carcinoma (ILC) (15%). Most patients had stage II (45%) or stage III (35%) breast cancer at the time of diagnosis. All patients underwent core needle biopsy for tumour grade evaluation. Conclusion: In conclusion, the study supports the use of core needle biopsy as a reliable method for evaluating tumour grade in breast cancer patients. Further research is needed to evaluate the long-term outcomes of patients who are treated based on tumour grade assessed by core needle biopsy.

Abstract OT1-07-01: Omission of SLNB in triple-negative and HER2-positive breast cancer patients with radiologic and pathologic complete response in the breast after NAST: a single-arm, prospective surgical trial (EUBREAST-01 trial, GBG 104)

Abstract Background: Currently, axillary surgery for breast cancer is considered a staging procedure that does not seem to influence breast cancer mortality since the risk of developing metastasis depends mainly on the biological behavior of the primary (seed-and-soil model). Based on this, postsurgical therapy should be considered based on biological tumor characteristics. Retrospective data of cancer registry trials showed a strong correlation between breast pathologic complete response (pCR) and nodal pCR depending on intrinsic subtypes. Improvements in systemic treatments for breast cancer have increased the rates of pCR in patients receiving neoadjuvant systemic therapy (NAST), offering the opportunity to decrease, and perhaps eliminate, surgery in patients who have a pCR. Trial design: The EUBREAST network designed a clinical trial (NCT04101851) in which only patients with the highest likelihood of having a pCR after NAST (triple-negative or HER2-positive breast cancer) will be included, and type of surgery will be defined according to the response to NAST rather than on the classical T and N status at presentation. In the ongoing trial, axillary surgery will be eliminated (no axillary sentinel lymph node biopsy [SLNB]) for initially clinical node-negative (cN0) patients with radiologic complete remission (rCR) and a breast pCR (ypT0/ypTis) as determined in the lumpectomy specimen. The trial design is a multicenter single-arm study with a limited number of patients (N=440 as the screening population with an expected 80% pCR-rate) which might give practice-changing results in a short period, sparing the time and the costs of a randomized comparison. Patients will be recruited in European countries (Austria, Germany, Italy, and Spain) over 36 months. Inclusion criteria: -Written informed consent -Histologically confirmed unilateral primary invasive carcinoma of the breast (core biopsy). Multifocal or multicentric tumors are allowed if breast-conserving surgery (BCS) is planned. -Age at diagnosis at least 18 years -imaging techniques with estimated tumor stage between cT1-T3 before NAST -triple-negative (TNBC) or HER2-positive invasive breast cancer -TNBC is defined by: ER-negative (< 10% positive cells in IHC) and PgR-negative (< 10% positive cells in IHC), HER2-negative -clinically and sonographically tumor-free axilla before core biopsy (cN0/iN0) -in cases with cN0 and iN+, a negative core biopsy or fine-needle aspiration biopsy of the sonographically suspected lymph node is required -no evidence for distant metastasis (M0) -standard NAST with rCR -planned BCS with postoperative external whole-breast irradiation (conventional fractionation or hypofractionation) Primary objective: 3-year rate of axillary recurrence-free survival (ARFS) after BCS Statistics: The calculated total case number for per-protocol analysis is N=350, and the expected total number of screened patients is N=440. The assumption for acceptable 3-year ARFS ≥98.5% in the experimental arm is based on previous study findings. Timelines: -First patient in: January 2021 -Last patient in: December 2023 -Primary outcome analysis: Q1/2027 Current accrual: In June 2022, 150 patients were recruited in Germany and Italy. Contact: Prof. Dr. Toralf Reimer (eubreast-01@kliniksued-rostock.de), study chair Dr. Oreste D. Gentilini (gentilini.oreste@hsr.it), study co-chair Funding by Else Kroener-Fresenius Foundation, German Society of Senology, University of Rostock (Germany), and San Raffaele Hospital (Milan, Italy) Citation Format: Toralf Reimer, Thorsten Kuehn, Angrit Stachs, Anke Kleine-Tebbe, Nikola Bangemann, Andrea Stefek, Carolin Hammerle, Jörg Heil, Antje Nixdorf, Gabriele Bonatz, Agnieszka Nolte, Isabel T. Rubio, Florentia Peintinger, Keyur Mehta, Sibylle Loibl, Edoardo Botteri, Oreste Davide Gentilini. Omission of SLNB in triple-negative and HER2-positive breast cancer patients with radiologic and pathologic complete response in the breast after NAST: a single-arm, prospective surgical trial (EUBREAST-01 trial, GBG 104) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-07-01.

Abstract PD15-04: PD15-04 Overall survival following breast conserving surgery and adjuvant radiotherapy compared with mastectomy for early stage breast cancer: a systematic review and meta-analysis

Abstract Background Breast conserving surgery with adjuvant radiotherapy (BCS+RT) and mastectomy are currently offered as oncologically equivalent options for the surgical management of early breast cancer based on findings from randomised controlled trials (RCTs) conducted over four decades ago. Since then, locoregional and systemic breast cancer treatments have improved significantly and several recent observational studies suggest a survival advantage in patients receiving BCS+RT compared to those having mastectomy. If BCS+RT is oncologically superior to mastectomy, this may dramatically impact surgical treatment recommendations. The aim of this systematic review was to identify, critically appraise and summarise the contemporary literature comparing survival following BCS+RT and mastectomy to inform surgical decision-making for patients with early breast cancer. Methods A systemic search of MEDLINE, Cochrane Central Register of Controlled Trials and Embase identified studies published between 1st January 2000 to 22nd September 2021. Included were primary research studies published in English comparing overall survival in women undergoing primary surgery with either BCS+RT or mastectomy for unilateral stage I to III breast cancer. Excluded were studies evaluating neoadjuvant chemotherapy; rare breast cancer subtypes (e.g. mucinous) or in specific patient populations (e.g. pregnancy associated breast cancer) and those that completed recruitment before 1st January 1990. We used the ROBINS-I tool to assess the risk of bias in study results and GRADE to assess the overall certainty of evidence. All papers without critical risk of bias were included in a quantitative meta-analysis. Where more than one study reported outcomes in overlapping population-based registry cohorts, the study with the most recent data on the largest cohort was selected for analysis. The primary analysis was a random effects meta-analysis with a fixed effect model undertaken as sensitivity analysis. A secondary meta-analysis was performed for studies only including triple negative breast cancers. All analyses were conducted using STATA17. Results 10,876 abstracts were screened and 157 full-text papers assessed for eligibility, of which 93 (17 multi-centre observational studies, 30 were single-centre observational studies and 46 registry-based studies) met the inclusion criteria for the review. 25 papers were excluded from meta-analysis due to an overall critical risk of confounder bias and 27 were excluded due overlapping study populations. 36 studies (34 with serious risk of bias and 2 with moderate risk of bias) reporting survival outcomes on 1,321,291 patients (729,789 undergoing BCS+RT and 591,502 undergoing mastectomy) were included in the meta-analysis. The pooled hazard ratio was 0.72 (95% CI 0.64– 0.81, p< 0.001, I2 97.6%) demonstrating improved overall survival for patients undergoing BCS+RT compared with those receiving mastectomy. The sensitivity analysis, using a fixed effect model, showed a hazard ratio of 0.88 (95% CI 0.87 – 0.89, p< 0.001, I2 97.6%) for survival in women undergoing BCS+RT compared with mastectomy. Meta-analysis of 8 studies reporting survival in 17,181 patients with triple negative breast cancer showed a hazard ratio of 0.73 (95% CI 0.68 – 0.79), p< 0.001, I2 34.7%) for those receiving BCS+RT versus mastectomy. Discussion This meta-analysis provides further, albeit very low certainty evidence, that overall survival is improved following BCS+RT compared with mastectomy in a contemporary cohort of patients treated for early-stage breast cancer. These results should be interpreted with caution due to the heterogeneity of included studies and the high risk of bias associated with observational data. As future RCTs will not be feasible, well-designed large-scale prospective observational studies are needed to provide better evidence to support surgical decision-making in early-stage breast cancer. Citation Format: Kiran Kasper Rajan, Katherine Fairhurst, Beth Birkbeck, Rebecca Wilson, Jelena savovic, Chris Holcombe, Shelley Potter. PD15-04 Overall survival following breast conserving surgery and adjuvant radiotherapy compared with mastectomy for early stage breast cancer: a systematic review and meta-analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD15-04.

The role of anthracycline and pertuzumab in preoperative treatment of HER2-positive breast cancer

Polychemotherapy combined with trastuzumab (T) or trastuzumab with pertuzumab (TP) is a standard preoperative systemic treatment in patients with HER2-positive breast cancer. In Poland T is reimbursed according to the Drug Prescription Program of Ministry of Health (MoH) for patients with primary breast tumors bigger than 1cm independently from nodal status, whereas TP is reimbursed for patients with tumors bigger than 2 cm with positive lymph node(s) or lack of hormonal receptors expression. The Drug Prescription Program does not indicate which polychemotherapy should be combined with anti-HER2 therapy. Therefore, one can choose between classical sequential treatment based on anthracycline and taxane combined with T or dual HER2 blockade (usually 4 × AC → 12 × paclitaxel/4 × docetaxel + T/TP), or docetaxel with carboplatin combined with trastuzumab (TCH) or with dual HER2 blockade (TCHP). According to the present guidelines of the National Comprehensive Cancer Network (NCCN), polychemotherapy without anthracycline is preferred, which is justified because of its lower toxicity, especially cardiotoxicity. Currently, a pathologically confirmed complete response (pCR) is usually the primary objective in clinical trials dedicated to preoperative systemic treatment in breast cancer. pCR became a surrogate of treatment effectiveness. That is why oncologists eagerly use polychemotherapy combined with dual HER2 blockade as preoperative treatment to increase the patient’s chance to achieve pCR, sometimes even when the patient’s risk of relapse is relatively small. The goal of this article is to review current evidence-based knowledge about the effectiveness and toxicity of polychemotherapy with or without anthracycline combined with trastuzumab or dual HER2 blockade used as preoperative treatment in HER2-positive breast cancer patients.