Menstrual cycle could affect Ki67 expression in estrogen receptor-positive breast cancer patients

Horimoto, Yoshiya; Arakawa, Atsushi; Tanabe, Masahiko; Kuroda, Keiji; Matsuoka, Joe; Igari, Fumie; Himuro, Takanori; Yoshida, Yuko; Tokuda, Emi; Shimizu, Hideo; Hino, Okio; Saito, Mitsue

doi:10.1136/jclinpath-2015-203085

Cited by 10 publications

(10 citation statements)

References 19 publications

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“…So, in our study, the correction rate of hot spot lesions by core-needle biopsy may have been markedly influenced if the tumor size was larger because the materials by core-needle biopsy were more localized. Fur-Open Journal of Obstetrics and Gynecology [21]. In our study, there was no correlation between the hormone receptor status and the discrepancy of the Ki-67-labeling index between core-needle samples and surgical specimens.…”

Section: Discussioncontrasting

confidence: 51%

Favorable Reproducibility of Ki-67-Labeling Index between Core Needle Biopsy and Surgical Materials in Mammary Carcinoma: Reproducibility Influenced by Hot Spots, a High Ki-67 Labeling Index, and the Total Length of Biopsy Material

Ogura¹,

Matsumoto²,

Sakaguchi³

et al. 2018

OJOG

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Aims: The reproducibility of Ki-67 between core-needle biopsies and surgical materials has not been well documented in the literature, although the concordance affects the utility of the Ki-67 labeling index based on the core-needle biopsy materials, which indicates the need for preoperative chemotherapy. The aim of this study was to reveal the reproducibility of Ki-67 between both materials and the cause of discrepancies. Methods and Results: We analyzed 137 cases of invasive carcinoma of the breast and the compared Ki-67-labeling index between core-needle biopsy and surgical materials. The Ki-67-labeling index of biopsy and surgical specimens ranged from 1% to 85% (median: 13%) and 1% to 80% (median: 12%), respectively. The discrepancy of Ki-67-labeling ranged from 0% to 55% (median: 4%) and could be calculated by the tumor size, hot spots of surgical materials, a high Ki-67-labeling index based on the core-needle biopsy materials, and the total length of core needles, respectively. Conclusions: The concordance rate of the Ki-67-labeling index between core-needle biopsies and surgical materials was favorable, so we can use each Ki-67-labeling index of core-needle biopsies as a marker for preoperative chemotherapy. Factors affecting the index discrepancy were hot spots, a high Ki-67-labeling index, and the total length of biopsy material. Judgements on the subtypes and clinical procedures of invasive breast carciHow to cite this paper: Ogura, K., Matsumoto, T., Sakaguchi, A., Onagi, H., Ura, A., Kosaka, T., Kitabatake, T., Kojima, K. and Morizane, T. (2018)

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Section: Discussioncontrasting

confidence: 51%

Favorable Reproducibility of Ki-67-Labeling Index between Core Needle Biopsy and Surgical Materials in Mammary Carcinoma: Reproducibility Influenced by Hot Spots, a High Ki-67 Labeling Index, and the Total Length of Biopsy Material

Ogura¹,

Matsumoto²,

Sakaguchi³

et al. 2018

OJOG

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“…The observed variability in younger women could be a factor of menstrual cycling, as previous studies report that tumour proliferation and HER2 gene expression fluctuate during the menstrual cycle, in accordance with concentrations of oestrogen and progesterone. In premenopausal women, the highest proliferative activity of breast epithelium [28] and breast cancer samples [29] is observed during the luteal phase, when circulating concentrations of progesterone peak. Additionally, in vitro and in vivo stimulation with oestrogen and/or progesterone promotes proliferation of breast cancer cells, an effect which can be reversed with anti-estrogenic treatment [30,31].…”

Section: Discussionmentioning

confidence: 99%

Discordance in 21-gene recurrence scores between paired breast cancer samples is inversely associated with patient age

et al. 2020

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Background: The Oncotype DX 21-gene Recurrence Score is a genomic-based algorithm that guides adjuvant chemotherapy treatment decisions for women with early-stage, oestrogen receptor (ER)-positive breast cancer. However, there are age-related differences in chemotherapy benefit for women with intermediate Oncotype DX Recurrence Scores that are not well understood. Menstrual cycling in younger women is associated with hormonal fluctuations that might affect the expression of genomic predictive biomarkers and alter Recurrence Scores. Here, we use paired human breast cancer samples to demonstrate that the clinically employed Oncotype DX algorithm is critically affected by patient age. Methods: RNA was extracted from 25 pairs of formalin-fixed paraffin-embedded, invasive ER-positive breast cancer samples that had been collected approximately 2 weeks apart. A 21-gene signature analogous to the Oncotype DX platform was assessed through quantitative real-time PCR, and experimental recurrence scores were calculated using the Oncotype DX algorithm. Results: There was a significant inverse association between patient age and discordance in the recurrence score. For every 1-year decrease in age, discordance in recurrence scores between paired samples increased by 0.08 units (95% CI − 0.14, − 0.01; p = 0.017). Discordance in recurrence scores for women under the age of 50 was driven primarily by proliferation-and HER2-associated genes. Conclusion: The Oncotype DX 21-gene Recurrence Score algorithm is critically affected by patient age. These findings emphasise the need for the consideration of patient age, particularly for women younger than 50, in the development and application of genomic-based algorithms for breast cancer care.

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“…We speculate that differences in serum estradiol levels according to age might be one of the factors impacting these effects, though the mechanism is unknown. We further investigated premenopausal patients in Groups A and B (3 and 9 patients, respectively) to determine whether they were in the luteal phase on the day of surgery, since we previously observed a Ki67 labelling index increase in patients who were menstruating 19 . Interestingly, the proportion of patients in the luteal phase in Group B was higher than that in Group A (66% and 33%, respectively), although the number of patients examined was too small to allow meaningful conclusions to be drawn.…”

Section: Discussionmentioning

confidence: 99%

Elucidation of inhibitory effects on metastatic sentinel lymph nodes of breast cancer during One-Step Nucleic Acid Amplification

Horimoto

Tanabe

Kazuno

et al. 2018

Sci Rep

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One-step nucleic acid amplification (OSNA) is an established method for intraoperative diagnosis of breast cancer metastasis in sentinel lymph nodes, based on quantification of CK19 mRNA, specific to breast epithelial cells. Inhibitors interfere with the PCR amplification process of PCR. Thus, OSNA, based on gene amplification without RNA purification, might be impacted by numerous factors persisting in a sample, and thereby potentially acting as PCR inhibitors. However, neither the characteristics of breast cancers showing inhibitory effects during OSNA, nor any of the possible inhibitors, have as yet been identified. Inhibitory effects detected during OSNA in 72 metastatic lymph nodes and the patients’ clinicopathological features were examined. Left-over OSNA samples were analyzed with mass spectrometry to identify proteins possibly acting as inhibitors. Most tumors showed inhibitory effects, though to varying degrees. Large tumor, young age and high tumor-infiltrating lymphocyte counts were related to stronger inhibitory effects. Proteome analysis revealed elevations in RPB9 protein and EIF2 signaling upregulation in samples showing strong inhibitory effects. Tumors showing strong inhibitory effects had clinically relevant characteristics, including large size and extensive tumor-infiltrating lymphocyte involvement. Identifying inhibitors in OSNA might provide new insights into breast cancer biology as well as advancing the current technology.

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Menstrual cycle could affect Ki67 expression in estrogen receptor-positive breast cancer patients

Cited by 10 publications

References 19 publications

Favorable Reproducibility of Ki-67-Labeling Index between Core Needle Biopsy and Surgical Materials in Mammary Carcinoma: Reproducibility Influenced by Hot Spots, a High Ki-67 Labeling Index, and the Total Length of Biopsy Material

Favorable Reproducibility of Ki-67-Labeling Index between Core Needle Biopsy and Surgical Materials in Mammary Carcinoma: Reproducibility Influenced by Hot Spots, a High Ki-67 Labeling Index, and the Total Length of Biopsy Material

Discordance in 21-gene recurrence scores between paired breast cancer samples is inversely associated with patient age

Elucidation of inhibitory effects on metastatic sentinel lymph nodes of breast cancer during One-Step Nucleic Acid Amplification

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