Breast cancer is the second largest cancer in the world, and it has highest mortality rate in women worldwide. The aberrant activation of the cyclin-dependent kinase 4 and 6 (CDK4/6) pathway plays an important role in uncontrolled breast cancer cell proliferation. Therefore, targeting CDK4/6 to improve overall survival rates has been a strong interest in breast cancer therapeutics. Till date, four CDK4/6 inhibitors have been developed and approved for hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer therapies with great success. However, acquired resistance to CDK4/6 inhibitors has emerged and limits their effectiveness in breast cancer. In this review, we systematically discussed the mechanisms of resistance to CDK4/6 inhibitors including the cell cycle-specific and cell cycle-nonspecific mechanisms. Also, we analyzed combination strategies with other signaling inhibitors in clinical and preclinical settings that further expand the clinical application of CDK4/6 inhibitors in future breast cancer therapies.

The objective of this systematic review is to investigate the role of imaging in response monitoring during neoadjuvant systemic therapy (NST) for breast cancer and assess whether treatment modifications based on imaging response are implemented in clinical practice.

A systematic review was conducted, analyzing five clinical practice guidelines and 147 clinical trial publications involving NST for breast cancer. The snowballing technique was employed, using a "start set" of clinical guidelines to trace relevant trials. Additionally, a PubMed search was conducted to identify trials published between 2023-2024. The review analyzed the use of imaging modalities, timing, and response criteria, and whether escalation, de-escalation, or change of treatment occurred based on imaging response.

Imaging was utilized in 81 % (119/147) of the trials, with ultrasound, MRI, and mammography being the most frequently employed modalities. Mid-treatment imaging was applied in 56 % (83/147) of the trials. However, only 15 % (22/147) of the trials implemented treatment modifications based on imaging response, highlighting the limited application of imaging response-guided therapy. No standardized imaging protocols or consistent response-guided treatment strategies were identified across the trials or clinical practice guidelines, with considerable variability in imaging methods, timing, and response criteria.

This systematic review underscores the critical need for standardized imaging protocols, response assessment criteria and image-guided treatment decisions. It is therefore evident that imaging for response monitoring during treatment should preferably be performed within clinical trials.

Cell-cycle protein-dependent kinase 4 and 6 inhibitors (CDK4/6is) in combination with endocrine therapy (ET) are widely used in patients with early and advanced breast cancer (BC). CDK4/6is also lead to numerous side effects. This study aims to elucidate the relationship between CDK4/6is and hepatotoxicities.

As of 31 March 2024, we conducted a systematic search of PubMed, Embase, and the Cochrane Library databases, as well as several oncology conference proceedings. We included 20 randomized controlled trials (RCTs) with 24,342 breast cancer (BC) patients and 400 cases from the FDA Adverse Event Reporting System (FAERS). Fixed-effect and random-effect models were used to calculate odds ratios (ORs) of hepatotoxicity in the RCTs, while Reporting Odds Ratios (RORs) were calculated for the FAERS data.

Overall, CDK4/6 inhibitors (CDK4/6is) were associated with significant hepatotoxicities compared to controls (OR = 1.76, 95%CI 1.40-2.22, I2 = 75%). Palbociclib, ribociclib, and abemaciclib exhibited significant hepatotoxicities, while dalpiciclib did not. FAERS data showed significant liver enzyme and organ toxicity signals for ribociclib and abemaciclib but not for palbociclib.

CDK4/6is increase the risk of hepatotoxicities in patients with BC. Palbociclib, ribociclib, and abemaciclib caused liver damage, while dalpiciclib did not. The most common manifestations were elevated ALT and AST levels.

This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)- locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)-computed tomography (CT) and metabolites with efficacy.

Fulvestrant and EC-T regimen were given to ER+/HER2- LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography-mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety.

Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways.

This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

Invasive lobular breast cancer (ILC) presents unique challenges and considerations in the realm of surgical management. Characterized by its distinct histological features, including the loss of E-cadherin expression and dys-cohesive growth pattern, ILC often poses diagnostic and therapeutic dilemmas for clinicians. This abstract explores the surgical landscape of ILC, focusing on its epidemiology, clinical presentation, diagnostic modalities, and surgical interventions. Emphasizing the importance of individualized treatment strategies, this narrative delves into the nuances of surgical decision-making, including the role of breast-conserving surgery versus mastectomy, axillary staging, and the significance of margin status. Additionally, advancements in surgical techniques, such as oncoplastic approaches and sentinel lymph node biopsy, are examined in the context of optimizing oncologic outcomes and preserving cosmesis. Through a comprehensive review of current literature and clinical guidelines, this overview aims to provide a nuanced understanding of the surgical considerations inherent to the management of invasive lobular breast cancer.

The objective of this study is to assess the efficacy and safety of combining goserelin with anastrozole in neoadjuvant endocrine therapy (NET) for patients diagnosed with premenopausal breast cancer.

A retrospective analysis was conducted on the clinicopathological data of 34 patients diagnosed with premenopausal breast cancer who underwent NET in the Department of Breast Surgery at Baotou Cancer Hospital between March 2016 and December 2019. Additionally, the feasibility of using goserelin combined with anastrozole for premenopausal endocrine therapy was assessed.

The duration of NET ranged from 6 to 72 months, with a mean of 22.5 months and a median of 18 months. In patients with progressive disease, endocrine therapy was assessed over a period of 6 to 18 months, with a mean of 13.1 months and a median of 13 months. Among the 28 patients assessed, 12 (42.86%) were found to have stable disease, subsequently receiving chemotherapy. Of these, seven patients demonstrated good compliance, and 5 achieved a pathological complete response. Including the 2 patients who responded favorably to NET alone, a total of 7 patients attained a pathological complete response. Additionally, 16 patients achieved complete cell cycle arrest following treatment. A significant correlation was observed between the clinical efficacy assessment and the pathological assessment of NET (P < 0.05).

Although NET was safe for patients diagnosed with premenopausal breast cancer, it should not be considered in isolation from chemotherapy. Transitioning to chemotherapy in a timely manner can significantly enhance treatment outcomes. The duration of NET should be guided by clinical assessment rather than being constrained by a predetermined time frame.

The management of early breast cancer (BC) has witnessed an uprise in the use of neoadjuvant therapy and a remarkable reshaping of the systemic therapy postneoadjuvant treatment in the last few years, with the evolution of many controversial clinical situations that require consensus.

During the 14th Breast-Gynecological and Immuno-Oncology International Cancer Conference held in Egypt in 2022, a panel of 44 BC experts from 13 countries voted on statements concerning debatable challenges in the neo/adjuvant treatment setting. The recommendations were subsequently updated based on the most recent data emerging. A modified Delphi approach was used to develop this consensus. A consensus was achieved when ≥75% of voters selected an answer.

The consensus recommendations addressed different escalation and de-escalation strategies in the setting of neoadjuvant therapy for early BC. The recommendations recapitulate the available clinical evidence and expert opinion to individualize patient management and optimize therapy outcomes. Consensus was reached in 63% of the statements (52/83), and the rationale behind each statement was clarified.

The role of combining neoadjuvant endocrine therapy with conventional chemotherapy remains unclear; therefore, we conducted an open-label, single-center, nonrandomized phase II trial to assess the effect of this combination. Patients with previously untreated stage II or III HR-positive, HER2-negative breast cancer received concurrent letrozole 2.5 mg with standard neoadjuvant chemotherapy. The primary endpoint was pathologic complete response (pCR) at the time of surgery. We used Simon's minimax two-stage design; a pCR rate > 6% was necessary at the first stage to continue. Between November 2017 and November 2020, 53 women were enrolled in the first stage of the trial. Their median age was 49 years (range, 33-63), and 60% of them were premenopausal. Subsequently, 66% and 34% of patients with clinical stages II and III, respectively, were included; 93% had clinically node-positive disease. Two patients (4%) achieved pCR after neoadjuvant chemo-endocrine treatment, which did not satisfy the criteria for continuing to the second stage. The overall response rate was 83%. During the median follow-up of 53.7 months, the 3-year disease-free survival and overall survival rates were 87% and 98%, respectively. Neutropenia was the most common grade 3/4 adverse event (40%), but rarely led to febrile neutropenic episodes (4%). Myalgia (32%), nausea (19%), constipation (17%), heartburn (11%), oral mucositis (9%), and sensory neuropathy (9%) were frequently observed, but classified as grade 1 or 2. No deaths occurred during preoperative treatment. The addition of letrozole to standard neoadjuvant chemotherapy was safe and beneficial in terms of overall response rate, but did not provide a higher pCR rate in locally advanced HR-positive, HER2-negative breast cancer. Further research is needed to enhance neoadjuvant treatment strategies for this cancer subtype.

Neoadjuvant endocrine therapy presents an important downstaging option with lower toxicity than neoadjuvant chemotherapy in oestrogen receptor (ER)-positive early breast cancer. Meta-analysis of the effects of neoadjuvant endocrine therapy on surgical outcomes across randomized clinical trials (RCTs) and cohort studies has not previously been performed.

A systematic review and meta-analysis was performed to evaluate the effect of neoadjuvant endocrine therapy on surgical outcomes (PROSPERO (international prospective register of systematic reviews, 2020)) compared with surgery followed by adjuvant endocrine therapy. PubMed and EMBASE were searched to identify RCT and cohort studies between 1946 and 27 March 2024. Two independent reviewers manually screened the identified records and extracted the data. Risk of bias was assessed using the Cochrane Collaboration tools and random-effects meta-analysis was done with ReviewManager.

The search identified 2390 articles eligible for screening. The review included 20 studies (12 cohort and 8 RCTs); 19 were included in the meta-analysis with a total of 6382 patients. Overall, neoadjuvant endocrine therapy was associated with a lower mastectomy rate compared with surgery first (risk ratio (RR) 0.53, 95% c.i. 0.44 to 0.64). Subgroup analysis showed similar improvement in the mastectomy rate in the neoadjuvant endocrine therapy group versus control group irrespective of study type (RCT: RR 0.58, 95% c.i. 0.50 to 0.66; cohorts: RR 0.48, 95% c.i. 0.33 to 0.70). There was no difference in the mastectomy rate by duration of neoadjuvant endocrine therapy (more than 4 months: RR 0.57, 95% c.i. 0.42 to 0.78; 4 months or less than 4 months: RR 0.52, 95% c.i. 0.43 to 0.64). Most of the studies were characterized by moderate-quality evidence with significant heterogeneity.

Neoadjuvant endocrine therapy is associated with a reduction in mastectomy rate. Given the moderate methodological quality of previous studies, further RCTs are required.

CRD42020209257.

Navigating the complex landscape of breast cancer treatment involves distinct strategies for luminal and triple-negative subtypes. While neoadjuvant chemotherapy historically dominates the approach for aggressive triple-negative tumors, recent evidence highlights the transformative impact of immunotherapy, alongside chemotherapy, in reshaping treatment paradigms. In luminal cancers, endocrine therapy, notably aromatase inhibitors, demonstrates promising outcomes in postmenopausal patients with low-grade luminal A tumors. However, integrating targeted therapies like CDK4/6 inhibitors in neoadjuvant setting remains inconclusive. Identifying predictive factors for treatment response, especially in luminal tumors, poses a challenge, emphasizing the necessity for ongoing research. A multidisciplinary approach, tailored to individual patient profiles, is crucial for maximizing efficacy while minimizing toxicity. As we strive to optimize breast cancer management, a comprehensive understanding of the distinct characteristics and treatment implications of luminal and triple-negative subtypes, including the transformative role of immunotherapy, is essential for informed decision-making and personalized care.

Neoadjuvant treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer is controversial and requires a comprehensive analysis for optimal therapy assessment. Therefore, a two-step Bayesian network meta-analysis (NMA) was performed to compare the efficacy and safety of different neoadjuvant regimens.

Phase II/III randomized clinical trials comparing various neoadjuvant therapies for HR+/HER2- breast cancer were included. NMA and pairwise meta-analyses were conducted using Stata (version 14), R (version 4.2.3), and Review Manager 5.4.

Twenty-eight studies (5,625 patients) were eligible. NMA of objective response rate (ORR) indicated the highest SUCRA for chemotherapy (CT) and chemotherapy with anthracycline (CT(A)). Pathologic complete response (PCR) NMA demonstrated significant PCR improvement with chemotherapy regimens containing programmed cell death protein-1 and programmed cell death ligand-1 inhibitors (PD-1i/PD-L1i) and poly ADP-ribose polymerase inhibitors (PARPi). Combined analysis considering both the ORR and safety highlighted CT(A)'s efficacy and toxicity balance.

CT(A) and CT showed improved ORR compared with alternative regimens. CT(A) combined with PD-1/PD-L1 or PARP inhibitors significantly increased PCR rates. Comprehensive assessment of both ORR and safety indicated that CT(A) represents an optimal neoadjuvant therapy for HR+/HER2- breast cancer, whereas AI + CDK4/6 inhibitors rank solely behind chemotherapy.

PROSPERO Registration: CRD42024538948. International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) registration number INPLASY202440092.

To assess the efficacy of neoadjuvant endocrine therapy in female HR-positive/HER2-negative breast cancer patients.

We identified female patients aged ≥18 years with cT1-4N0-XM0, HR(+), and HER2(-) breast cancer from the National Cancer Database. The patients who underwent surgery first were categorized as "surgery-first," while those who received NET before surgery were classified as "NET." Propensity score-matching, Cox proportional-hazard model, variance inflation factors, and interaction analysis were employed to estimate the correlation between NET and survival outcomes.

Among 432,387 cases, 2914 NET patients and 2914 surgery-first patients were matched. Compared with the surgery-first group, the NET group received less adjuvant chemotherapy (p < 0.001). Furthermore, the NET group exhibited higher survival probabilities compared with the surgery-first group (3 years: 91.4% vs. 82.1%; 5 years: 82.1% vs. 66.8%). Multivariate Cox analysis indicated that NET was associated with improved OS (surgery-first vs. NET: HR 2.17, 95% CI: 1.93-2.44). Age over 55 years old, having public insurance, higher CDCC score, higher NSBR grade, ER(+)PR(-), and advanced clinical stage were related to worse OS (all p < 0.05). There was an interaction between age, race, income, and home and treatment regimen (all p < 0.05).

NET may be a more effective treatment procedure than surgery-first in female HR-positive/HER2-negative, non-metastatic breast cancer patients. Future clinical studies with more detailed data will provide higher-level evidence-based data.

For HR-positive/HER2-negative patients who can undergo breast-conserving surgery (BCS) but have a tumor size of 2-5 cm or 1-3 lymph node metastases, neoadjuvant chemotherapy (NAC) is still controversial.

Patients with T2N0-1M0 HR-positive/HER2-negative BC who underwent BCS between 2010 and 2017 were selected from the SEER database. Propensity score matching (PSM) was used to minimize the influence of confounding factors. The overall survival (OS) and breast cancer-specific survival (BCSS) of patients were estimated by Kaplan‒Meier curves and Cox proportional hazard models. Independent prognostic factors were included to construct a nomogram prediction model.

A total of 6475 BC patients were enrolled, of whom 553 received NAC and 5922 received adjuvant chemotherapy (AC). In the T2N0-1M0 population and T2N1M0 subgroup, AC patients before PSM had better OS and BCSS than NAC patients. After PSM, there was no significant difference in OS or BCSS between the two groups. However, in the T2N0M0 subgroup, there was no difference in survival between the AC and NAC groups before and after PSM. Stratified analysis revealed that for complete response (CR) patients, survival was roughly equivalent between the NAC and AC groups. However, the survival of no response (NR) and partial response (PR) patients was significantly worse than that of AC patients. Cox analysis revealed that radiotherapy after BCS was an independent protective factor for OS. NAC is an independent risk factor for NR and PR patients. The nomogram has good prediction efficiency.

NAC before BCS is not necessary for T2N0-1M0 HR-positive/HER2-negative BC patients.

Patients with locally advanced endocrine positive tumors who will not benefit from chemotherapy can be treated by either primary surgery or neoadjuvant endocrine therapy (NET). How often does NET result in breast-conserving surgery (BCS)?

We conducted a literature search in PubMed and Embase, to identify articles on surgical treatment after NET.

In 19 studies the pathological complete response (pCR) rate was reported after NET; an overall pCR rate of 1% was found. Compared with neoadjuvant chemotherapy (NCT), the BCS rate was significantly higher after NET (OR 0.60; 95% CI, 0.51-0.69; P < 0.00001). The surgical conversion rate was reported in eight studies [4-75.9%], with a mean of 30.2%.

This review found that one out of three patients becomes eligible for BCS after treatment with NET.

Neoadjuvant endocrine therapy (NAE) offers a breast-conserving surgery rate and clinical response rate similar to those of neoadjuvant chemotherapy (NAC), while presenting fewer adverse events and lower pathological complete response rates. The assessment of pathological response determines degenerative changes and predicts the prognosis of breast cancer treated with NAC. This study clarified the degenerative changes occurring in breast cancer following NAE.

Our study encompassed two groups: NAE, consisting of 15 patients, and NAC, comprising 18 patients. Tissue samples were obtained from core needle biopsies and surgeries. Nuclear and cell areas were calculated using Autocell analysis. Furthermore, we assessed markers associated with microtubule depolymerization (KIF2A) and initiators of apoptosis (caspase-9).

In the NAC group, we observed significant increases in both cytoplasmic and cell areas. These changes in cytoplasm and cells were notably more pronounced in the NAC group compared to the NAE group. After treatment, KIF2A exhibited a decrease, with the magnitude of change being greater in the NET group than in the NAC group. However, no discernible differences were found in caspase-9 expression between the two groups.

Our findings indicate that NAE induces condensation in cancer cells via cell cycle arrest or apoptosis. Conversely, NAC leads to cell enlargement due to the absence of microtubule depolymerization. These discrepancies underscore the importance of accounting for these distinctions when establishing criteria for evaluating pathological responses.

Photodynamic therapy (PDT) is increasingly used in modern medicine. It has found application in the treatment of breast cancer. The most common cancer among women is breast cancer. We collected cancer cells from the breast from the material received after surgery. We focused on tumors that were larger than 10 mm in size. Breast cancer tissues for this quantitative non-contrast magnetic resonance imaging (MRI) study could be seen macroscopically. The current study aimed to present findings on quantitative non-contrast MRI of breast cancer cells post-PDT through the evaluation of relaxation times. The aim of this work was to use and optimize a 1.5 T MRI system. MRI tests were performed using a clinical scanner, namely the OPTIMA MR360 manufactured by General Electric HealthCare. The work included analysis of T1 and T2 relaxation times. This analysis was performed using the MATLAB package (produced by MathWorks). The created application is based on medical MRI images saved in the DICOM3.0 standard. T1 and T2 measurements were subjected to the Shapiro-Wilk test, which showed that both samples belonged to a normal distribution, so a parametric t-test for dependent samples was used to test for between-sample variability. The study included 30 sections tested in 2 stages, with consistent technical parameters. For T1 measurements, 12 scans were performed with varying repetition times (TR) and a constant echo time (TE) of 3 ms. For T2 measurements, 12 scans were performed with a fixed repetition time of 10,000 ms and varying echo times. After treating samples with PpIX disodium salt and bubbling with pure oxygen, PDT irradiation was applied. The cell relaxation time after therapy was significantly shorter than the cell relaxation time before PDT. The cells were exposed to PpIX disodium salt as the administered pharmacological substance. The study showed that the therapy significantly affected tumor cells, which was confirmed by a significant reduction in tumor cell relaxation time on the MRI results.

Neoadjuvant therapy is commonly used in patients with locally advanced or inoperable breast cancer (BC). Neoadjuvant chemotherapy (NACT) represents an established treatment modality able to downstage tumours, facilitate breast-conserving surgery, yet also achieve considerable pathologic complete response (pCR) rates in HER2-positive and triple-negative BC. For patients with HR+/HER2- BC, the choice between NACT and neoadjuvant endocrine therapy (NET) is still based on clinical and pathological features and not guided by biomarkers of defined clinical utility, differently from the adjuvant setting where gene-expression signatures have been widely adopted to drive decision-making. In this review, we summarize the evidence supporting the choice of NACT vs NET in HR+/HER2- BC, discussing the issues surrounding clinical trial design and proper selection of patients for every treatment. It is time to question the binary paradigm of responder vs non-responders as well as the "one size fits all" approach in luminal BC, supporting the utilization of continuous endpoints and the adoption of tissue and plasma-based biomarkers at multiple timepoints. This will eventually unleash the full potential of neoadjuvant therapy which is to modulate patient treatment based on treatment sensitivity and surgical outcomes. We also reviewed the current landscape of neoadjuvant studies for HR+/HER2- BC, focusing on antibody-drug conjugates (ADCs) and immunotherapy combinations. Finally, we proposed a roadmap for future neoadjuvant approaches in HR+/HER2- BC, which should be based on a staggered biomarker-driven treatment selection aiming at impacting long-term relevant endpoints.

Genomic instability is one of the well-established hallmarks of cancer. The homologous recombination repair (HRR) pathway plays a critical role in correcting the double-stranded breaks (DSB) due to DNA damage in human cells. Traditionally, the BRCA1/2 genes in the HRR pathway have been tested for their association with breast cancer. However, defects in the HRR pathway (HRD, also termed 'BRCAness'), which has up to 50 genes, have been shown to be involved in tumorigenesis and treatment susceptibility to poly-ADP ribose polymerase inhibitors (PARPis), platinum-based chemotherapy, and immune checkpoint inhibitors (ICIs). A reliable consensus on HRD scores is yet to be established. Emerging evidence suggests that only a subset of breast cancer patients benefit from ICI-based immunotherapy. Currently, albeit with limitations, the expression of programmed death-ligand 1 (PDL1) and tumor mutational burden (TMB) are utilized as biomarkers to predict the favorable outcomes of ICI therapy in breast cancer patients. Preclinical studies demonstrate an interplay between the HRR pathway and PDL1 expression. In this review, we outline the current understanding of the role of HRD in genomic instability leading to breast tumorigenesis and delineate outcomes from various clinical trials. Furthermore, we discuss potential strategies for combining HRD-targeted therapy with immunotherapy to achieve the best healthcare outcomes in breast cancer patients.

Breast cancer (BC) remains a significant health care challenge, and treatment approaches continue to evolve. Among these, neoadjuvant endocrine therapy (NET) has gained prominence, particularly for postmenopausal, hormone-receptor positive, HER2-negative (HR+/HER2-) BC patients. Despite this, a significant gap exists in identifying patients who stand to benefit from NET. The objective of this study was to assess whether Magee equations (MEs) could serve as predictors of response to NET.

This retrospective study included adult patients with invasive BC who underwent NET followed by curative surgery. Assessment of sociodemographic, clinical, and tumor-related variables was conducted. The ME1, ME2, ME3, and ME mean were analyzed to explore their predictive role for NET response. Receiver operating characteristic (ROC) curves were employed, along with the determination of optimal cutoff points. Logistic regression models were utilized to identify the most significant predictors of pathological response.

Among the 75 female participants, the mean age was 69.4 years, with the majority being postmenopausal (n = 72, 96%) and having an ECOG-PS of 0/1 (n = 63, 84%). Most patients were classified as luminal A (n = 41, 54.7%). ME3 emerged as a promising predictor, boasting an AUC of 0.734, with sensitivity of 90.62% and specificity of 57.50% when the threshold was ≤ 19.97. In univariate analysis, clinical staging (p = 0.002), molecular subtype (p = 0.001), and ME3 (continuous = 0.001, original 3-tier: p = 0.013, new 2-tier: <0.001) categories exhibited significant associations with pathological response. In the multivariate model, clinical staging and new 2-tier ME3 (<20 vs. ≥20) were included as significant variables.

Patients with ME3 < 20 have a higher likelihood of presenting a pathological response, offering a cost-effective alternative tool to Oncotype DX. Larger future studies with a prospective design are awaited to confirm our findings.

Neoadjuvant endocrine therapy (NET) is recommended for the treatment of invasive breast cancer (BC), particularly luminal subtypes, in locally advanced stages. Previous randomized studies have demonstrated the benefits of aromatase inhibitors in this context. However, NET is typically reserved for elderly or frail patients who may not tolerate neoadjuvant chemotherapy. Identifying non-responsive patients early and extending treatment for responsive ones would be ideal, yet optimal strategies are awaited.

This non-randomized phase 2 clinical trial aims to assess NET feasibility and efficacy in postmenopausal stage II and III luminal BC patients, identifying predictive therapeutic response biomarkers. Efficacy will be gauged by patients with Ki67 ≤ 10% after 4 weeks and Preoperative Endocrine Prognostic Index (PEPI) scores 0 post-surgery. Study feasibility will be determined by participation acceptance rate (recruitment rate ≥50%) and inclusion rate (>2 patients/month).

Postmenopausal women with luminal, HER2-tumors in stages II and III undergo neoadjuvant anastrozole treatment, evaluating continuing NET or receiving chemotherapy through early Ki67 analysis after 2 to 4 weeks. The study assesses NET extension for up to 10 months, using serial follow-ups with standardized breast ultrasound and clinical criteria-based NET suspension. Clinical and pathological responses will be measured overall and in the luminal tumor A subgroup. Toxicity, health-related quality of life, and circulating biomarkers predicting early NET response will also be evaluated.

Although mucinous carcinoma (MC) is considered a favorable histologic subtype of invasive breast cancer (BC), a subset of MC is managed with neoadjuvant therapy (NAT). The clinical and pathologic features of MC following NAT are not well characterized. The aim of this study is to characterize pathologic response in patients with MC treated with NAT, including neoadjuvant endocrine therapy (NET), neoadjuvant chemotherapy (NCT), and Herceptin-targeted NCT (H-NCT). We conducted a retrospective cohort study of 28 patients with MC who received preoperative adjuvant therapy followed by resection from three institutions between 2010 and 2020. Demographic and clinical information were retrieved from the medical records. Pathologic review of the post NAT resection specimens was performed including tumor grading, tumor size, staging, residual tumor cellularity, estrogen receptor (ER) and HER2 status. Nine (32 %) patients with ER+/HER2- MC received NET, 8 (29 %) ER+/HER2- MC were treated with NCT only and 11 (39 %) HER2+ MC received HER2-targeted NCT (H-NCT). The HER2+ MC patients were younger (45 vs. 64 years; p = 0.006). The HER2+ MC were of higher grade (p = 0.03) and more likely to be multifocal (p = 0.008). Only 2 of 28 (7 %) MC (both HER2+) showed complete pathologic response with residual acellular mucin pools. Persistent mass-forming mucin pools were present in 26 (93 %) cases. The residual tumor cellularity was markedly reduced (≤5 %) in H-NCT treated MC (11/11, 100 %), followed by NET group (6/9, 67 %) and NCT only group (4/8, 50 %) (p = 0.011). Similarly, a higher rate of pathologic response (pCR/RCB-I) was observed in H-NCT (7/11, 64 %), followed by NET group (5/9, 56 %), and NCT only group (1/7, 13 %) (p = 0.053). Post-therapy, all HER2+ MC were smaller than 2 cm and ypT size was significantly smaller in H-NCT group (11/11, 100 %) versus combined NET (5/9, 55 %) and NCT only groups (4/8, 50 %) (p = 0.029). We conclude that ER-/HER2+ and ER+/HER2-mucinous carcinomas of the breast show robust pathological response to neoadjuvant HER2 targeted and endocrine therapy, respectively. Our findings suggest that MC may show good response to endocrine therapy.

Breast cancer is the most commonly diagnosed cancer and the leading cause of death among female patients, which seriously threatens the health of women in the whole world. The treatments of breast cancer require the cooperation of a multidisciplinary setting and taking tumor load and molecular makers into account. For early breast cancer, breast-conserving surgery with radiotherapy or mastectomy alone remains the standard management, and the administration of adjuvant systemic therapy is decided by the status of lymph nodes, hormone receptors, and human epidermal growth factor receptor-2. For metastatic breast cancer, the goal of treatments is to prolong survival and maintain quality of life. This review will present the current advances and controversies of surgery, chemotherapy, radiotherapy, endocrine therapy, targeted therapy, immunotherapy, gene therapy, and other innovative treatment strategies in early-stage and metastatic breast cancer.

In recent years, endocrine therapy (ET), an effective systemic treatment for the management of estrogen receptor (ER)-positive breast cancers, has regained interest as a neoadjuvant therapy based on evidence that ET can fulfill the aim of neoadjuvant systemic treatment for tumor shrinkage as well as elucidate important clinical information on endocrine sensitivity that enables the prognostication of patients. Moreover, neoadjuvant endocrine therapy (NET) potentially provides an opportunity for early assessment of the clinical efficacy of novel agents. Furthermore, recently reported trials have generated evidence for a more tailored approach for perioperative management of ER-positive breast cancer using clinical and molecular biomarkers, and this has provided a rationale that enables the broadening of clinical indications for NET. This review discusses the current evidence for NET, the evolution of NET trials, clinical indications, and NET-based treatment strategies.

Breast cancer is the leading cause of cancer in women in Spain and its annual incidence is rapidly increasing. Thanks to the screening programs in place, nearly 90% of breast cancer cases are detected in early and potentially curable stages, despite the COVID-19 pandemic possibly having impacted these numbers (not yet quantified). In recent years, locoregional and systemic therapies are increasingly being directed by new diagnostic tools that have improved the balance between toxicity and clinical benefit. New therapeutic strategies, such as immunotherapy, targeted drugs, and antibody-drug conjugates have also improved outcomes in some patient subgroups. This clinical practice guideline is based on a systematic review of relevant studies and on the consensus of experts from GEICAM, SOLTI, and SEOM.

Breast cancer treatment has evolved significantly over the years, both in terms of local and systemic approaches. Halsted's radical mastectomy gave way to modified mastectomies and to conservative surgeries, along with breast reconstruction and repair. Although the use of new drugs has directly increased the survival of patients submitted to adjuvant or neoadjuvant systemic therapies, the de-escalation of drugs may also be beneficial in numerous cases. Therefore, breast cancer treatment must be increasingly customized and assessed using a multidisciplinary approach. This study aimed to review the concept and therapy of early breast cancer.

A narrative review of the literature was carried out in the PubMed database in December 2022, where the keywords for the searches were as follows: early breast cancer, surgical treatment of breast cancer, systemic treatment of breast cancer, neoadjuvant chemotherapy in breast cancer, adjuvant treatment of luminal breast cancer, early triple negative tumor, and early positive Her-2 tumor. Articles that were historically important in the treatment of breast cancer and articles that impacted management with scientific relevance were selected for this review.

As new evidence continues to update existing knowledge, breast cancer treatment is becoming increasingly personalized and must now take into account the different tumor variants and their clinical stages, the age of patients and relevant comorbidities, as well as personal expectations and desires.

This literature review of current studies shows that the primary therapy for patients with early breast cancer continues to be surgery, although a customized and multidisciplinary approach is now required.

Disease progression during neoadjuvant systemic therapy for breast cancer indicates poor prognosis, while predictors of the clinical outcomes of these patients remain unclear. By comparing the clinical outcomes of patients with different patterns of salvage treatment strategies, we try to evaluate the factors predicting distant failure and explore the favourable treatment for them.

Patients with disease progression during neoadjuvant systemic therapy for stage I-III breast cancer diagnosed between January 1, 2008 and July 31, 2021 in Fudan University Shanghai Cancer Center were enrolled. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions or the appearance of new breast or nodal lesions. Kaplan-Meier, univariate and multivariate Cox proportional hazard regressions were utilized to compare survival outcomes between different salvage treatment strategies.

Among 3775 patients treated with NST, 60 (1.6%) patients encountered disease progression. A significant difference between the outcomes of patients receiving direct surgery and other salvage modalities was found (p = 0.007). Triple-negative breast cancer (p = 0.010) and not receiving direct surgery (p = 0.016) were independently associated with distant disease-free survival on multivariate analysis.

Predictors of distant failure in patients with disease progression include triple-negative breast cancer and not receiving direct surgery. Direct surgery seems to be more favourable than other treatments for patients with disease progression. For inoperable patients, neoadjuvant radiation can increase their operability but not improve their prognosis.

This study aimed to compare the efficacy of neoadjuvant systemic therapy (NST) with solvent-based paclitaxel (Sb-P), liposomal paclitaxel (Lps-P), nanoparticle albumin-bound paclitaxel (Nab-P), and docetaxel in human epidermal growth factor receptor 2 (HER2)-low-positive and HER2-zero breast cancers. A total of 430 patients receiving 2-weekly dose-dense epirubicin and cyclophosphamide (EC) followed by 2-weekly paclitaxel (Sb-P, Lps-P, or Nab-P), or 3-weekly EC followed by 3-weekly docetaxel for NST were enrolled in the study. In HER2-low-positive patients, the pathological complete response (pCR) rate in Nab-P group was significantly higher than that in the other three paclitaxel groups (2.8 % in Sb-P group, 4.7 % in Lps-P group, 23.2 % in Nab-P group and 3.2 % in docetaxel group, p < 0.001). In HER2-zero patients, the pCR rate did not differ significantly among the four paclitaxel groups (p = 0.278). The NST regimen containing Nab-P could be considered a promising treatment option in HER2-low-positive breast cancer.

The study's purpose was to evaluate the correlation between overall survival (OS) and its potential surrogate endpoints: pathologic complete response (pCR) and event-free survival (EFS)/disease-free survival (DFS) in neoadjuvant and/or adjuvant HR+/HER2- breast cancer.

Systematic search was performed in MEDLINE, EMBASE, Cochrane Library databases and other relevant sources to identify literature that have reported outcomes of interest in the target setting. The strength of correlation of EFS/DFS with OS, pCR with OS, and pCR with EFS/DFS was measured using Pearson's correlation coefficient (r) based on weighted regression analysis. For Surrogate Endpoint-True Endpoint pairs where correlation was found to be moderate, surrogate threshold effect (STE) was estimated using a mixed-effects model. Sensitivity analyses were conducted on the scale and weights used and removing outlier data.

Moderate correlation was observed of relative measures [log(HR)] of EFS/DFS and OS (r = 0.91; 95% CI: 0.83, 0.96, p < 0.0001). STE for HR_EFS/DFS was estimated to be 0.73. Association between EFS/DFS at 1, 2 and 3 years with OS at 4- and 5-year landmarks was moderate. Relative treatment effects of pCR and EFS/DFS were not strongly associated (r: 0.24; 95% CI: -0.63, 0.84, p = 0.6028). Correlation between pCR and OS was either not evaluated due to inadequate sample size (relative outcomes) or weak (absolute outcomes). Results obtained in the sensitivity analyses were similar to base scenario.

EFS/DFS were moderately correlated with OS in this trial-level analysis. They may be considered as valid surrogates for OS in HR+/HER2- breast cancer.

At present, there is no consensus on the required duration of neoadjuvant endocrine therapy (NET), yet there is no consistent conclusion on the factors influencing the efficacy of treatment with breast cancer after prolonged treatment.

To explore the effect of prolonged NET on the efficacy of patients with breast cancer and analyze the factors influencing the efficacy of treatment with breast cancer after the treatment duration is prolonged.

The case histories of 51 patients who were diagnosed with breast cancer and received NET in our hospital from September 2017 to December 2021 were retrospectively analyzed. All patients received NET for over 12 months. The clinical efficacy and tumor size changes after treatment for six months and 12 months were compared, and the factors influencing the efficacy of treatment with breast cancer after patients' treatment duration was prolonged were analyzed.

(1) Among the 51 patients, the objective remission rate (ORR) of NET, at T = 6 months was 21.6%, and the average tumor size was 15.52 ± 7.30 mm. The ORR of the NET at T = 12 months was 52.9%, and the average tumor size was 13.79 ± 7.43 mm. (2) After the treatment duration was prolonged, the clinical ORRs of patients with estrogen receptor (ER) (+) and progesterone receptor (PR) (+) were significantly higher than that of patients with ER (+) and PR (-) and patients with ER (-) and PR (+), which was (P < 0.05). (3) There was no significant difference between the patients' axillary lymph node status and the Ki67 expression before treatment and the clinical ORR after prolonged treatment, which was (P> 0.05).

(1) Prolonging the NET duration for patients with breast cancer can improve their clinical ORR and further reduce the tumor size, but patients' conditions should be closely monitored during the treatment process to prevent the progression of disease due to drug resistance. (2) The expression state of ER or PR may be used as a factor influencing the efficacy of treatment with breast cancer after prolonged treatment. (3) There was no significant effect on the patients' axillary lymph node status and the Ki67 expression before treatment on the clinical efficacy after prolonged treatment.

While endocrine therapy is the standard-of-care adjuvant treatment for hormone receptor-positive (HR+) breast cancers, there is also extensive evidence for the role of pre-operative (or neoadjuvant) endocrine therapy (NET) in HR+ postmenopausal women.

We conducted a thorough review of the published literature, to summarize the evidence to date, including studies of how NET compares to neoadjuvant chemotherapy, which NET agents are preferable, and the optimal duration of NET. We describe the importance of on-treatment assessment of response, the different predictors available (including Ki67, PEPI score, and molecular signatures) and the research opportunities the pre-operative setting offers. We also summarize recent combination trials and discuss how the COVID-19 pandemic led to increases in NET use for safe management of cases with deferred surgery and adjuvant treatments.

NET represents a safe and effective tool for the management of postmenopausal women with HR+/HER2- breast cancer, enabling disease downstaging and a wider range of surgical options. Aromatase inhibitors are the preferred NET, with evidence suggesting that longer regimens might yield optimal results. However, NET remains currently underutilised in many territories and institutions. Further validation of predictors for treatment response and benefit is needed to help standardise and fully exploit the potential of NET in the clinic.

Ovarian function suppression (OFS) is a potentially life-saving treatment for young women diagnosed with high-risk hormonal-receptor (HR)+ early breast cancer (EBC), albeit one associated with significant side effects that may adversely affect quality of life. Of particular concern, this article raises a few borderline indications that were largely unaddressed in pivotal clinical trials but are still commonly encountered in daily practice. These, referred to here as 'borderline indications of OFS' remain a source of uncertainty for patients and physicians and are concisely addressed in this article.

Despite neoadjuvant hormone therapy (NHT) is being underused, it is an effective treatment for luminal tumors at a lower cost and with fewer side effects compared to those associated with neoadjuvant chemotherapy (NCT). The lack of robust comparative data between NHT and NCT is a factor that limits its use in clinical practice.

This study will be a randomized, open-label, non-inferiority clinical trial. Patients diagnosed with HER2-negative luminal-subtype breast cancer will be identified at the time of diagnosis. Menopausal patients randomized for NHT should receive anastrozole for at least six months. Premenopausal women should receive anastrozole associated with subcutaneous goserelin acetate every 12 weeks for at least six months. Patients randomized for NCT will receive a standard institutional regimen based on anthracyclines and taxanes. Sample size was calculated considering the CPS + EG as a method for evaluating response and prognosis, where a score <3 was defined as good. The non-inferiority margin for NHT was set at 15%. The study considered a power of 80%, a significance level of 5%, and an outcome proportion in each group of 69%, resulting in 118 patients in each group. We estimated at 10% of losses, resulting in a sample of 130 patients in each group.

The non-inferiority of NHT in relation to NCT will provide further evidence that replacing NCT with NHT is safe and effective in eligible patients, which is particularly relevant for populations with limited access to health services and for institutions with few available resources.

Neoadjuvant endocrine therapy (NET) can be used to treat estrogen receptor positive (ER+) invasive breast cancer (IBC). Tumors with Ki67>10% after 2 to 4 weeks of NET are considered resistant to endocrine therapy. Enhancer of Zeste Homolog 2 (EZH2) is a targetable oncoprotein and overexpression in ER+ IBC has been linked to resistance to endocrine therapy. We examined whether EZH2 expression levels in ER+ IBC could be used to predict response to NET.

We retrospectively identified 46 patients with localized ER+ HER2/neu negative IBC treated with a minimum of 4 weeks of NET. We quantified EZH2 nuclear expression in pretherapy core biopsies using a score that included intensity and percent of cells staining. Ki67 was evaluated in both pretherapy core biopsies and posttherapy tumor resections and scored according to the guidelines of the International Ki67 Working Groups, with a global weighted score. Ki67≤10% after NET was considered endocrine responsive. Logistic regression analysis was performed to determine the association between EZH2 expression and response to NET.

We found significant associations of tumor grade ( P =0.011), pretherapy Ki67 ( P =0.003), and EZH2 ( P <0.001), with response to NET. On logistic regression adjusted for tumor grade and pretherapy Ki67, increased EZH2 scores were associated with decreased odds of endocrine responsiveness, defined as posttreatment Ki67≤10% (odds ratio=0.976, 95% CI, 0.956 to 0.997; P =0.026). In addition, with EZH2 score in the model, associations of tumor grade and pretreatment Ki67 with posttreatment Ki67≤10% response to NET became not significant.

Our results suggest that EZH2 might be a useful biomarker to predict response to NET.

There is growing interest in neoadjuvant endocrine therapy (NET) for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 -negative (HR + HER2-) breast cancer. Expanding the use of genomic assays demonstrates that many patients with HR + HER2-breast cancer do not benefit from chemotherapy, leading to growing interest in NET as a less toxic alternative. Although NET's ability to downsize breast tumors and achieve breast conservation is well-known, axillary surgery algorithms are not well-defined. Here we review primary endocrine therapy, the landmark NET clinical trials, and management of residual nodal disease following NET.

The role of neoadjuvant therapy (NAT) for localized breast cancer has evolved tremendously over the past several years. Currently, NAT is the preferred option for high-risk early triple-negative (TN) and HER2-positive (HER2+) breast cancers and is indicated for some estrogen receptor-positive (ER+) breast cancers. In addition to traditional absolute indications for NAT, relative indications such as the assessment of outcomes at the time of surgery and guidance of treatment escalation and de-escalation have greatly evolved in recent years. Pathologic complete response (pCR) and the Residual Cancer Burden (RCB) index are highly prognostic for disease recurrence and survival, mainly in patients with TN or HER2+ disease. Furthermore, post-NAT escalation strategies have been shown to improve long-term outcomes of patients who do not achieve pCR. Additionally, by allowing the direct assessment of drug effect on the tumor, the neoadjuvant setting has become an attractive setting for the exploration of novel agents and the identification of predictive biomarkers. Neoadjuvant trial design has also evolved, using adaptive treatment approaches that enable treatment de-escalation or escalation based on response. However, despite multiple practice-changing neoadjuvant trials and the addition of various new agents to the neoadjuvant setting for early breast cancer, many key questions remain. For example, patient selection for neoadjuvant immunotherapy in TN breast cancer, de-escalation methods in HER2+ breast cancer, and the use of gene expression profiles to guide NAT recommendations in ER+ breast cancer. This article reviews the current approach for NAT in localized breast cancer as well as evolving NAT strategies, the key remaining challenges, and the ongoing work in the field.

Although breast cancer is rare and understudied in adults age 40 and younger, recent epidemiologic data show an increasing incidence of breast cancer among young women in the United States and ongoing inferior long-term outcomes. Given breast cancers arising at a young age are more likely to present at advanced stages and to have aggressive biology, multimodal treatments are often indicated. Elevated local recurrence risks and greater propensity for germline cancer predisposition mutations can impact local therapy choices. Recently, escalated systemic therapy regimens for triple-negative breast cancer incorporating immunotherapy, de-escalated anti-HER2 therapy, and emerging targeted agents, including CDK4/6 inhibitors and PARP inhibitors, for early-stage disease may be employed in younger and older patients alike, with some special considerations. Prognostic genomic signatures can spare low-risk young women with hormone receptor-positive breast cancer adjuvant chemotherapy, but management of intermediate-risk patients remains controversial. Ovarian function suppression and extended endocrine therapy are improving outcomes in hormone receptor-positive breast cancer, but treatment adherence is a particular problem for young patients. Young women may also face greater challenges in long-term survivorship, including impaired fertility, difficulties in psychosocial adjustment, and other treatment-related comorbidities. Consideration of these age-specific issues through dedicated multidisciplinary strategies is necessary for optimal care of young women with breast cancer.

The combination of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors and endocrine treatment has benefited patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER + /HER2-) metastatic breast cancer; however, its effects in the neoadjuvant setting for ER + /HER2- early breast cancer (EBC) are unclear. Systematic searches were performed in PubMed, Embase, Cochrane Library, and major oncological meetings for trials of CDK4/6 inhibitors plus neoadjuvant endocrine treatment (NET) vs. NET/neoadjuvant chemotherapy (NACT) alone up to January 30, 2021. We assessed the efficacy of CDK4/6 inhibitors plus NET vs. NET/NACT alone in ER + /HER2- EBC. Six studies that included 803 patients treated with CDK4/6 inhibitors plus NET vs. NET/NACT alone were used. Compared with NET/NACT alone, CDK4/6 inhibitors plus NET increased the complete cell cycle arrest (CCCA) rate (OR, 9.00; 95% CI, 5.42-14.96; P < 0.001). Nonsignificant differences between CDK4/6 inhibitors and NET/NACT alone occurred in the preoperative endocrine prognostic index (PEPI)-0 rate (OR, 1.13; 95% CI, 0.59-2.18; P = 0.71), pathological complete response (pCR) rate (OR, 0.75; 95% CI, 0.13-4.29; P = 0.74), objective response rate (ORR) (OR, 0.70; 95% CI, 0.21-2.29; P = 0.55), and disease control rate (DCR) (OR, 1.16; 95% CI, 0.47-2.89; P = 0.74). CDK4/6 inhibitors plus NET indicated a high risk of neutropenia (OR, 56.43; 95% CI, 15.76-202.11; P < 0.001) as an adverse effect (AE) and elevated alanine aminotransferase (ALT) level (OR, 15.30; 95% CI, 2.02-115.98; P = 0.008) as grade 3/4 AEs. Compared with NET/NACT alone, CDK4/6 inhibitors plus NET increased CCCA rate in ER + /HER2- EBC patients. CDK4/6 inhibitors plus NET did not substantially improve the PEPI-0 rate, pCR rate, ORR, or DCR. The combination increased the risk of neutropenia and elevated ALT levels. In the neoadjuvant setting, addition of CDK4/6 inhibitors to NET may be an option for treating ER + /HER2- EBC.

Estrogen receptor (ER+) breast cancer is the most frequently diagnosed breast cancer subtype. Currently, adjuvant treatment for early stage disease consists of endocrine therapy, with or without chemotherapy and bone-targeted therapy, delivered in a risk-adapted manner. Despite this multimodal approach, a significant proportion of high risk patients will develop incurable distant recurrences. There is an ongoing need to develop new treatment strategies that address the biologic causes of treatment failure and to identify the individual patients who can benefit from such interventions. Here we review the clinical investigation of targeted and novel therapies, including inhibitors of the PI3K-AKT-mTOR pathway, oral selective estrogen receptor degraders (SERDs), and PARP-inhibitors for the treatment of early ER+ breast cancer. Furthermore, we highlight opportunities in biomarker development to help guide the delivery of escalated adjuvant strategies.

Breast cancer (BC) is the most common type of cancer diagnosed among women worldwide with an estimated 2.3 million new cases every year. Almost two-thirds of all patients with BC have estrogen receptor-positive (ER+) tumors. In this review, the clinical evidence of exemestane in different treatment settings in ER+ BC is presented and summarized.

A search strategy with the keywords "breast cancer [MeSH Terms]" AND "exemestane [Title/Abstract]" was devised and a search was performed in PubMed.

The efficacy of exemestane in different treatment settings has been established by numerous clinical studies. Exemestane is recommended as an adjuvant treatment in postmenopausal women previously treated with tamoxifen in trials comparing 5 years of tamoxifen with 2-3 years of tamoxifen combined with 2-3 years of exemestane, which proved that treatment with exemestane provided better survival outcomes. Similarly, exemestane could be considered as a safe treatment option for neoadjuvant treatment, prevention of chemotherapy, and treatment of advanced BC either alone or in combination with other targeted therapy drugs in both pre- and postmenopausal women.

Exemestane could be considered as a reasonable therapeutic option in the treatment of ER+ BC at any stage in pre- and postmenopausal women.

The present goal of therapy for early hormone receptor-positive (HR+)/human EGF receptor 2-negative (HER2-) BC is to optimize disease-free survival (DFS) and overall survival (OS) rates with the currently available therapies while avoiding any relevant long-term sequalae. Local therapies have evolved toward less aggressive techniques (i.e. breast-preserving surgery, sentinel lymph node biopsy and intraoperative radiotherapy), which significantly reduce the long-term sequalae observed with more radical treatments. Endocrine therapy (ET) is still the cornerstone of adjuvant treatment because it significantly reduces BC relapse and mortality. Adjuvant chemotherapy is today recommended only for a particular subset of patients with a high risk of recurrence with ET alone, identified through genomic assays, age and/or disease stage. Bisphosphonates reduce the risk of bone metastasis and produce a slight although statistically significant improvement in survival in postmenopausal women. The CDK 4/6 inhibitor abemaciclib has been recently approved by the US FDA for patients at high risk of relapse.

The ESR1 gene encodes Estrogen Receptor alpha (ERα), which plays a role in the tumourigenesis of breast cancer. A single nucleotide polymorphism (SNP) in intron 1 of this gene called ESR1 PvuII (rs2234693) has been reported to increase the risk of breast cancer. This study aimed to investigate the ESR1 PvuII polymorphism as a prognostic and predictive factor guiding the choice of therapy for advanced breast cancer.

This retrospective study was conducted in 104 advanced breast cancer patients at Dharmais Cancer Hospital from 2011 to 2018. The ESR1 PvuII polymorphism was analysed by Sanger sequencing of DNA from primary breast tumour samples.

The percentages of patients with ESR1 PvuII genotypes TT, TC, and CC were 42.3, 39.4, and 18.3%, respectively. Looking at prognosis, patients with ESR1 PvuII TC + CC had shorter overall survival than those with the TT genotype [HR = 1.79; 95% CI 1.05-3.04; p = 0.032]. As a predictive marker, TC + CC was associated with shorter survival (p = 0.041), but TC + CC patients on primary hormonal therapy had a median overall survival longer than TC + CC patients on primary chemotherapy (1072 vs 599 days).

The ESR1 PvuII TC + CC genotypes confer poor prognosis in advanced breast cancer, but these genotypes could be regarded as a good predictor of the therapeutic effect of hormonal treatment.