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Background/aim: Breast cancer remains a significant health challenge, with neoadjuvant chemotherapy (NACT) improving clinical outcomes in certain subtypes. However, the role of NACT in hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer is unclear due to various outcomes and generally low rates of pathologic complete response (pCR). This study introduces the Non-Luminal Disease Score (NOLUS) as a potential predictive tool for assessing the response to NACT in these cases., Patients and Methods: We retrospectively assessed patients diagnosed with locally advanced HR+/HER2- breast cancer who received NACT at our institution from 2009 to 2023. The study explored the association between NOLUS and pCR rates. NOLUS was calculated as positive or negative based on the percentage of estrogen receptor, progesterone receptor, and Ki-67 in tumor cells. We also investigated the correlation between pCR and invasive disease-free survival (iDFS), and examined NOLUS positivity across different age groups., Results: A total of 149 patients met the inclusion criteria. NOLUS-positive patients exhibited a significantly higher pCR rate of 33.33% compared to 10.4% in NOLUS-negative patients (p=0.0031). With a median follow-up of 2.47 years, NOLUS-positive patients who achieved pCR had a 100% iDFS rate, mirroring the pCR versus residual disease patterns seen in triple-negative patients. NOLUS positivity was observed in 20.43% of patients aged 22-50, compared to 8.93% in those over 50, though this difference was not statistically significant., Conclusion: NOLUS exhibits potential in predicting pCR in HR+/HER2- breast cancer, serving as a cost-effective substitute for genomic tests., Competing Interests: A-LA and GD declare no relevant conflict of interest. LK has received honoraria and consultancy fees from Ipsen, BMS, Janssen, MSD and Amgen. IN has received honoraria from Roche. KP has received honoraria and consultancy fees from MSD, Gilead, AstraZeneca, Novartis, Eli Lilly, Roche and GSK and Research Funding from Roche, Novartis, Daiichi Sankyo, Eli Lilly, AstraZeneca, BMS, Boehringer and EISAI., (©2024 The Author(s). Published by the International Institute of Anticancer Research.)

Background/aim: "HER2-low" is an emerging subtype of breast cancer, with a documented role in predicting response to treatment with novel antibody-drug conjugates. It is defined based on immunohistochemistry, but increasing evidence is challenging this approach as appropriate for identifying the HER2-low subgroup, due to both interobserver variability and limitations of the method itself., Patients and Methods: We retrospectively analyzed data from 430 patients from our departmental databases who had been subjected to an Oncotype-DX score and assessed the correlation of the Oncotype-DX HER2 single-gene score with the HER2 expression on immunohistochemistry. The Oncotype-DX Recurrence Score was also evaluated in the HER2-0 versus HER2-low subgroups., Results: The HER2 single-gene score was found to accurately correlate with the HER2 result on immunohistochemistry, with a statistically significant difference both between HER2-0 and HER2 +1 tumors (p<0.0001), as well as between HER2 +1 and +2 tumors (p<0.0001). There was no statistically significant difference in the recurrence score between the HER2-0 and the HER2-low subgroups., Conclusion: Oncotype-DX single-gene scores for HER2 are a potential surrogate marker for assessing the precise HER2 status, with better reproducibility and less interobserver variance compared to immunohistochemistry. The use of rt-PCR emerges as an alternative method of assessment of the HER2-low subgroup., Competing Interests: GD and TZ declare no relevant conflict of interest. LK has received honoraria and consultancy fees from Ipsen, BMS, Janssen, MSD and Amgen. IN has received honoraria from Roche. KP has received honoraria and consultancy fees from MSD, Gilead, AstraZeneca, Novartis, Eli Lilly, Roche and GSK., (©2024 The Author(s). Published by the International Institute of Anticancer Research.)

Background/aim: Low expression of HER2 has defined a new "HER2-low" subgroup of breast cancer with distinct clinicopathological characteristics and both prognostic and predictive implications. The impact of low HER2 expression in metastatic hormone receptor-positive HER2-negative breast cancer treated with first-line CDK4/6 inhibitors has not been studied. Using real-world patient data, we aimed to identify prognostic differences in this patient population according to HER2 expression with immunohistochemistry., Patients and Methods: We retrospectively analyzed 191 patients from 5 Oncology Department databases in Thessaloniki, Greece, with hormone receptor-positive HER2-negative metastatic breast cancer treated with CDK4/6 inhibitors in the first line, for whom detailed immunohistochemical HER2 data could be retrieved., Results: Median progression-free survival was numerically different among the different HER2 subgroups (3.35 years for HER2 0 tumors, 2.18 years for HER2 +1 tumors, 1.74 years for HER2 +2/ISH-negative tumors), but this difference was not statistically significant (p=0.477). Median PFS was statistically significantly longer in patients without visceral metastases (5.45 years) compared to patients with visceral metastases (1.61 years) (p=0.017). Median PFS was also statistically significantly longer in patients taking an aromatase inhibitor (2.99 years) compared to patients taking fulvestrant (1.33 years) (p<0.0001). There were no statistically significant differences in the other subgroups examined., Conclusion: CDK4/6 inhibitors are equally effective as first-line treatment agents, regardless of the exact level of HER2 expression. Numerical differences, however, do exist among the different HER2 subgroups, and merit further evaluation in future studies to better study this phenomenon., Competing Interests: GD declares no relevant conflict of interest. GK has received honoraria and consultancy fees from Amgen, Avaviosis, Astellas, AstraZeneca, Boehringer, BMS, Demo, Galenica, Ipsen, LEO Pharma, Merck, MSD, Novartis, Pfizer, Roche, and Sanofi. EL has received honoraria and consultancy fees from AstraZeneca, Genesis Pharma, Novartis, Pfizer, Roche, and Amgen. IK has received honoraria and consultancy fees from Boehringer, Sandoz, Amgen, Roche, AstraZeneca, Pfizer, Novartis, Sanofi, MSD, Merck and BMS. IB has received honoraria and consultancy fees from Sandoz, Amgen, Roche, AstraZeneca, Ipsen, Pfizer, Novartis, Sanofi, Genesis Pharma, MSD, LEO pharma, Merck, Servier and BMS and Research Funding from Boehringer, Regeneron, Eli Lilly, Pfizer, Novartis, BMS, MSD and Roche. KP has received honoraria and consultancy fees from MSD, Gilead, AstraZeneca, Novartis, Eli Lilly, Roche and GSK and Research Funding from Roche, Novartis, Daiichi Sankyo, Eli Lilly, AstraZeneca, BMS, Boehringer and EISAI., (Copyright 2022, International Institute of Anticancer Research.)

Background/aim: A possible role of antibody-drug conjugates against tumors with low HER2-expression, leads to the emergence of a new "low-HER2" classification in breast cancer, encompassing tumors from the hormonal-receptor-positive and the triple-negative subgroups. There is a need for data (clinical trial data and real-world evidence) that will accurately describe this population, the risk of recurrence and the possible benefit of HER2 targeted therapies., Patients and Methods: We retrospectively analyzed 949 patients from our Department databases, with hormonal receptor-positive and HER2-negative early breast cancer, for whom detailed data for immunohistochemical HER2-staining could be retrieved., Results: HER2-low expression was detected in 66.6% of patients (472 IHC +1 and 160 IHC +2 and ISH-negative). Lobular, or mixed lobular and ductal cancers had a statistically significantly lower chance of being HER2-low when compared to pure infiltrative ductal carcinomas (53.1% vs. 69.3% respectively). HER2-low status was not prognostic for recurrence-free survival or response to neoadjuvant chemotherapy. There was a non-significant trend for increased risk of recurrence for HER2-low, compared to HER2-0, in patients with lobular or mixed lobular and ductal carcinomas (HR=2.192, 95% CI=0.819-5.912)., Conclusion: Low expression of HER2 in hormonal receptor-positive early breast cancer does not affect prognosis but may lead to a shorter progression-free-survival in lobular and mixed ductal and lobular cancers. Despite optimal management, a large proportion of hormonal receptor-positive patients will relapse. Targeting HER2 in HER2-low cancers may offer a potential additional treatment strategy to improve survival of this group., Competing Interests: GD, EM, AI and TZ declare no relevant conflict of interest. LK has received honoraria and consultancy fees from Ipsen, BMS, Janssen, MSD and Amgen. IN has received honoraria from Roche. KP has received honoraria and consultancy fees from MSD, Gilead, AstraZeneca, Novartis, Eli Lilly, Roche, and GSK., (Copyright 2022, International Institute of Anticancer Research.)