The Role of Sentinel Lymph Node Biopsy in Breast Cancer Patients Who Become Clinically Node-Negative Following Neo-Adjuvant Chemotherapy: A Literature Review.

BACKGROUND: In clinically node-positive (cN+) breast cancer (BC) patients who become clinically node-negative (cN0) following neoadjuvant chemotherapy (NACT), sentinel lymph node biopsy (SLNB) after lymphatic mapping with lymphoscintigraphy is not widely accepted; therefore, it has become a topic of international debate. OBJECTIVE: Our literature review aims to evaluate the current use of this surgical practice in a clinical setting and focuses on several studies published in the last six years which have contributed to the assessment of the feasibility and accuracy of this practice, highlighting its importance and oncological safety. We have considered the advantages and disadvantages of this technique compared to other suggested methods and strategies. We also evaluated the role of local irradiation therapy after SLNB and state-of-the-art SLN mapping in patients subjected to NACT. METHODS: A comprehensive search of PubMed and Cochrane was conducted. All studies published in English from 2018 to August 2023 were evaluated. RESULTS: Breast units are moving towards a de-escalation of axillary surgery, even in the NACT setting. The effects of these procedures on local irradiation are not very clear. Several studies have evaluated the oncological outcome of SLNB procedures. However, none of the alternative techniques proposed to lower the false negative rate (FNR) of SLNB are significant in terms of prognosis. CONCLUSIONS: Based on these results, we can state that lymphatic mapping with SLNB in cN+ BC patients who become clinically node-negative (ycN0) following NACT is a safe procedure, with a good prognosis and low axillary failure rates.

Efficacy of Alternative Dose Regimens of Exemestane in Postmenopausal Women With Stage 0 to II Estrogen Receptor-Positive Breast Cancer: A Randomized Clinical Trial.

Importance: Successful therapeutic cancer prevention requires definition of the minimal effective dose. Aromatase inhibitors decrease breast cancer incidence in high-risk women, but use in prevention and compliance in adjuvant settings are hampered by adverse events. Objective: To compare the noninferiority percentage change of estradiol in postmenopausal women with estrogen receptor-positive breast cancer given exemestane, 25 mg, 3 times weekly or once weekly vs a standard daily dose with a noninferiority margin of -6%. Design, Setting, and Participants: This multicenter, presurgical, double-blind phase 2b randomized clinical trial evaluated 2 alternative dosing schedules of exemestane. Postmenopausal women with estrogen receptor-positive breast cancer who were candidates for breast surgery were screened from February 1, 2017, to August 31, 2019. Blood samples were collected at baseline and final visit; tissue biomarker changes were assessed from diagnostic biopsy and surgical specimen. Biomarkers were measured in different laboratories between April 2020 and December 2021. Interventions: Exemestane, 25 mg, once daily, 3 times weekly, or once weekly for 4 to 6 weeks before surgery. Main Outcomes and Measures: Serum estradiol concentrations were measured by solid-phase extraction followed by liquid chromatography-tandem mass spectrometry detection. Toxic effects were evaluated using the National Cancer Institute terminology criteria, and Ki-67 was assessed by immunohistochemistry. Results: A total of 180 women were randomized into 1 of the 3 arms; median (IQR) age was 66 (60-71) years, 63 (60-69) years, and 65 (61-70) years in the once-daily, 3-times-weekly, and once-weekly arms, respectively. In the intention-to-treat population (n = 171), the least square mean percentage change of serum estradiol was -89%, -85%, and -60% for exemestane once daily (n = 55), 3 times weekly (n = 56), and once weekly (n = 60), respectively. The difference in estradiol percentage change between the once-daily and 3-times-weekly arms was -3.6% (P for noninferiority = .37), whereas in compliant participants (n = 153), it was 2.0% (97.5% lower confidence limit, -5.6%; P for noninferiority = .02). Among secondary end points, Ki-67 and progesterone receptor were reduced in all arms, with median absolute percentage changes of -7.5%, -5.0%, and -4.0% for Ki-67 in the once-daily, 3-times-weekly, and once-weekly arms, respectively (once daily vs 3 times weekly, P = .31; once daily vs once weekly, P = .06), and -17.0%, -9.0%, and -7.0% for progesterone receptor, respectively. Sex hormone-binding globulin and high-density lipoprotein cholesterol had a better profile among participants in the 3-times-weekly arm compared with once-daily arm. Adverse events were similar in all arms. Conclusions and Relevance: In this randomized clinical trial, exemestane, 25 mg, given 3 times weekly in compliant patients was noninferior to the once-daily dosage in decreasing serum estradiol. This new schedule should be further studied in prevention studies and in women who do not tolerate the daily dose in the adjuvant setting. Trial Registration: ClinicalTrials.gov Identifier: NCT02598557; EudraCT: 2015-005063-16.

Alternative dosing of exemestane in postmenopausal women with ER-positive breast cancer. Design and methods of a randomized presurgical trial.

INTRODUCTION: Aromatase inhibitors are effective in lowering breast cancer incidence among postmenopausal women, but adverse events represent a barrier to their acceptability and adherence as a preventive treatment. This study aims to assess whether lowering exemestane schedule may retain biological activity while improving tolerability in breast cancer patients. METHODS/DESIGN: We are conducting a, pre-surgical, non-inferiority phase IIb study in postmenopausal women with newly diagnosed estrogen receptor-positive breast cancer. Participants are randomized to receive either exemestane 25 mg/day or 25 mg/three times-week or once a week for 4 to 6 weeks prior to surgery. The primary endpoint is the percentage change of serum estradiol concentration between baseline and surgery comparing the three arms. Sample size of 180 women was calculated assuming a 6% non-inferiority of the percent change of estradiol in the lower dose arms compared with the 80% decrease predicted in the full dose arm, with 80% power and using a one-sided 5% significance level and a two-sample t-test. Main secondary outcomes are: safety; change in Ki-67 in cancer and adjacent pre-cancer tissue, circulating sex hormones, adipokines, lipid profile, insulin and glucose changes, in correlation with drug and metabolites concentrations. RESULTS AND DISCUSSION: The present paper is focused on methodology and operational aspects of the study. A total of 180 participants have ben enrolled. The trial is still blinded, and the analyses are ongoing. Despite the short term duration, results may have relevant implications for clinical management of women at increased risk of developing a ER positive breast cancer.