The Present and Future of Neoadjuvant Endocrine Therapy for Breast Cancer Treatment

Martí, Covadonga; Sánchez-Méndez, José Ignacio

doi:10.3390/cancers13112538

Cited by 16 publications

(16 citation statements)

References 126 publications

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“…Specifically, Ki67 ≤ 10% after 2 to 4 weeks of NET has been used in several trials as a marker of response to NET and has been shown to correlate with both radiographic response to NET and with improved breast cancer outcomes. 10,12,15,40 Although the use of Ki67 to guide therapeutic decisions has previously been hampered by lack of analytical validity of the Ki67 assay, the International Ki67 in Breast Cancer Working Group has developed a standardized methodology for scoring Ki67, which was utilized in our study. 28 Selecting patients with HR+ tumors most likely to respond to NET is both challenging and critically important.…”

Section: Discussionmentioning

confidence: 99%

“…Effective NET induces cell cycle arrest; hence reduction in the percentage of Ki67-positive tumor cells, as measured by immunohistochemistry, is used as a measure of endocrine responsiveness. Specifically, Ki67 ≤10% after 2 to 4 weeks of NET has been used in several trials as a marker of response to NET and has been shown to correlate with both radiographic response to NET and with improved breast cancer outcomes 10,12,15,40. Although the use of Ki67 to guide therapeutic decisions has previously been hampered by lack of analytical validity of the Ki67 assay, the International Ki67 in Breast Cancer Working Group has developed a standardized methodology for scoring Ki67, which was utilized in our study 28…”

Section: Discussionmentioning

confidence: 99%

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EZH2 Protein Expression in Estrogen Receptor Positive Invasive Breast Cancer Treated With Neoadjuvant Endocrine Therapy: An Exploratory Study of Association With Tumor Response

Gan

Makower

et al. 2022

Applied Immunohistochemistry &Amp; Molecular Morphology

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Introduction: 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. Materials and Methods: 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. Results: 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. Conclusions: Our results suggest that EZH2 might be a useful biomarker to predict response to NET.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

EZH2 Protein Expression in Estrogen Receptor Positive Invasive Breast Cancer Treated With Neoadjuvant Endocrine Therapy: An Exploratory Study of Association With Tumor Response

Gan

Makower

et al. 2022

Applied Immunohistochemistry &Amp; Molecular Morphology

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“…Endocrine therapy refers to drugs to block the promoting effect of sex hormones on breast cancer cells according to the expression of ER and PR in breast cancer tissue [ 30 ]. Anastrozole is a potent, selective aromatase inhibitor of triazole, blocking estrogen biosynthesis by inhibiting aromatase [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Ovarian tissue cryopreservation in a patient with breast cancer during pregnancy: a case report

Cheng

Ruan

et al. 2021

J Ovarian Res

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Background Fertility preservation using ovarian tissue cryopreservation (OTC) in patients with certain diseases, especially those needing chemo- or radiotherapy, is becoming routine in various Western countries. Our hospital is the first and until now the only centre in China to use this method. The question of whether treatment of breast cancer during pregnancy (PrBC) should be similar to non-pregnant young patients with breast cancer is controversial. To our knowledge, this is the first report worldwide to use OTC as fertility preservation for PrBC. Case presentation During the 29th week of pregnancy, a 24-year-old woman underwent needle aspiration cytology of a left breast tumour. Ultrasound and cytology revealed BI-RADS 4a grade. Oncologists recommended termination of the pregnancy. Caesarean section was performed at week 32, and ovarian tissue samples were collected for OTC to preserve fertility and ovarian endocrine function. Twenty-three ovarian cortex slices were cryopreserved. It is estimated that 13,000 follicles were cryopreserved. Breast nodules and sentinel lymph node biopsy suggested invasive micropapillary carcinoma. Neoadjuvant chemotherapy was started within 1 week after diagnosis. After six courses of neoadjuvant chemotherapy, targeted drug therapy and goserelin acetate, left mastectomy and left axillary lymph node dissection were performed. In total, 23 doses of radiotherapy, eight trastuzumab targeted therapy treatments, and 17 pertuzumab + trastuzumab double targeted therapy treatments were performed after breast cancer surgery. Until now, more than 2 years after delivery, the ovarian function still is good, and no signs of a negative impact of OTC have been observed. Goserelin acetate injections, administered every 28 days, are planned to last for the next 5 years. In addition, endocrine therapy with anastrozole was started after breast cancer surgery and also is scheduled for 5 years. Conclusion OTC for fertility preservation in patients with PrBC does not delay breast surgery, radiotherapy or chemotherapy, which is essential for effective treatment of breast cancer. We assess this method as a promising fertility preservation method which was used here for the first time worldwide in a patient who developed breast cancer during pregnancy.

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“…The systematic therapy for ER-positive breast cancer includes both chemotherapy and endocrine therapy, which can be given in adjuvant and neoadjuvant settings. Neoadjuvant chemotherapy (NCT), neoadjuvant endocrine therapy (NET), and neoadjuvant sequential endocrine-chemotherapy (NECT) have been used in ER-positive breast cancer for almost two decades mostly to downstage tumors before breast-conserving surgery (BCS) [ 2 ]. Compared with NCT, NET has less cytotoxicity and is currently applied in older patients and patients with ER-rich tumors which are defined with an “Allred score” greater than 5 [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Biomarker Alteration after Neoadjuvant Endocrine Therapy or Chemotherapy in Estrogen Receptor-Positive Breast Cancer

Long

You

Song

et al. 2022

Life

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In estrogen receptor (ER)-positive breast cancer, changes in biomarker expression after neoadjuvant therapy indicate the therapeutic response and are prognostic. However, there is limited information about the biomarker alteration caused by neoadjuvant endocrine therapy in ER-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. We recruited ER-positive/HER2-negative breast cancer patients who received neoadjuvant chemotherapy (NCT), neoadjuvant endocrine therapy (NET), or sequential neoadjuvant endocrine-chemotherapy (NECT) at Peking University Cancer Hospital from 2015 to 2021. A total of 579 patients had paired immunohistochemistry information in both diagnostic biopsy samples and post-neoadjuvant therapy surgical samples. Through a paired comparison of the immunohistochemical information in pre-treatment and post-treatment samples, we found that progesterone receptor (PR) expression reductions were more frequent than ER expression reductions (70.8% vs. 35.2%) after neoadjuvant therapy. The percentage of patients who had a decreased Ki-67 index in the post-operative samples was similar in the three groups (79.8% vs. 79.7% vs. 78.4%). Moreover, PR losses caused by NET were related to low baseline PR expression (p = 0.001), while we did not find a significant association between PR losses and Ki-67 reductions (p = 0.428) or ER losses (p = 0.274). All three types of neoadjuvant therapies caused a reduction in ER, PR, and Ki-67 expression. In conclusion, we found that PR loss after NET was only significantly related to low baseline PR expression, and there is no significant difference in the extent of prognostic factor change including Ki-67 and ER between the PR loss and non-loss groups.

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The Present and Future of Neoadjuvant Endocrine Therapy for Breast Cancer Treatment

Cited by 16 publications

References 126 publications

EZH2 Protein Expression in Estrogen Receptor Positive Invasive Breast Cancer Treated With Neoadjuvant Endocrine Therapy: An Exploratory Study of Association With Tumor Response

EZH2 Protein Expression in Estrogen Receptor Positive Invasive Breast Cancer Treated With Neoadjuvant Endocrine Therapy: An Exploratory Study of Association With Tumor Response

Ovarian tissue cryopreservation in a patient with breast cancer during pregnancy: a case report

Biomarker Alteration after Neoadjuvant Endocrine Therapy or Chemotherapy in Estrogen Receptor-Positive Breast Cancer

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