The Proper Ki-67 Cut-Off in Hormone Responsive Breast Cancer: A Monoinstitutional Analysis with Long-Term Follow-Up

Lombardi, A.; Lazzeroni, Rachele; Bersigotti, Laura; Vitale, V.; Amanti, C.

doi:10.2147/bctt.s305440

Cited by 21 publications

(13 citation statements)

References 13 publications

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“…The ER and PR status was reported as negative or positive, using a cut off at 10% stained cells, according to the Dutch treatment guidelines 48 . The Ki-67 expression for this cohort was categorized as low (≤ 10%), intermediate (11-25%) or high (≥ 26%) [49][50][51] . For this study, tissue microarrays were immunohistochemically stained with the 4B5 anti-HER-2/neu antibody (Ventana Bench-Mark ULTRA, ROCHE), using cell lines and human tissues as internal controls.…”

Section: Tissue Microarray Scoringmentioning

confidence: 99%

HER2-low breast cancer shows a lower immune response compared to HER2-negative cases

Ende

Smid

Timmermans

et al. 2022

Sci Rep

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Currently, the human epidermal growth factor receptor 2 (HER2) status of breast cancer is classified dichotomously as negative or positive to select patients for HER2-targeted therapy. However, with the introduction of novel treatment options, it is important to get more insight in the biology of cancers with low HER2 expression. Therefore, we studied several clinicopathologic characteristics in relation to the level of HER2 expression (HER2- versus HER2low). We used a well-documented cohort of breast cancer patients (n = 529), with available tissue microarrays and Affymetrix mRNA expression data. HER2 status was scored as negative (immunohistochemistry 0) or low (immunohistochemistry 1 + or 2 + without amplification). We associated HER2 status with several clinicopathologic characteristics, gene-expression data and survival, stratified for estrogen receptor (ER) status. Overall, breast cancers were scored as HER2- (n = 429) or HER2low (n = 100). Within the ER+ cohort (n = 305), no significant associations were found between the HER2 groups and clinicopathologic features. However, HER2low tumors showed several differentially expressed genes compared to HER2- cases, including genes that are associated with worse outcome and depletion of immunity. In ER- cases (n = 224), HER2low status was significantly associated with increased regional nodal positivity, lower density of tumor infiltrating lymphocyte and a lower protein expression of Ki-67 and EGFR compared to HER2- cases. After multivariate analysis, only density of tumor infiltrating lymphocytes remained significantly associated with HER2low status (P = 0.035). No difference in survival was observed between HER2low and HER2- patients, neither in the ER+ nor ER- cohort. In conclusion, our data suggests that HER2low breast cancer is associated with a lower immune response compared to HER2- breast cancer.

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Section: Tissue Microarray Scoringmentioning

confidence: 99%

HER2-low breast cancer shows a lower immune response compared to HER2-negative cases

Ende

Smid

Timmermans

et al. 2022

Sci Rep

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“…In 13/15 cases the patients were ER+/Pr+; one patient was Er+/Pr−; one patient was Er−/Pr−. Ki 67 was considered positive if ≥ 20% [ 9 ]. Ki 67 was positive in only 3 cases.…”

Section: Resultsmentioning

confidence: 99%

Ductal carcinoma in situ of the male breast: clinical radiological features and management in a cancer referral center

Nicosia

Lissidini

Sargenti

et al. 2022

Breast Cancer Res Treat

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Purpose To present an overview of the management of male patients with Ductal Carcinoma In Situ of the breast (male DCIS). Methods We retrospectively studied all male patients with a diagnosis of pure DCIS from January 1999 to December 2018: 20 patients were identified in our cancer referral center. We collected data regarding clinical presentation, age of onset, radiological features, receptor status of the neoplasm, histological type, and the follow-up of those patients. Results The median age was 62 years (range 21–80). All patients underwent surgery, in 15/20 (75%) cases a mastectomy was carried out. Two patients (10%) underwent endocrine treatment and 1/20 (5%) underwent radiotherapy. The receptor status for 15/20 patients was documented: 13/15 patients were ER+/Pr+. In 3 cases the Ki 67% was positive (i.e., > 20%). All cases were negative for Her2. The median follow-up time was 9.0 years (IQR 4.0–13.7). Only one patient had an ipsilateral recurrence with the finding of an infiltrating carcinoma in the same breast after 14 years. The 5-year disease-free survival was 92.9%. Conclusion Pure DCIS in men is an extremely rare disease: proper diagnosis and management allow an excellent prognosis.

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“…At the latest St Gallen meeting in 2021, 42.4% of the experts suggested the threshold for Ki-67 to recommend adjuvant chemotherapy in ER+, HER2-, node-negative breast cancer is 30% [14] .Many studies have taken different threshold to explore the effect of Ki-67 expression on the prognosis, which including 14% [15] , 15% [16] , 22% [17] , 25% [18] . Some studies have pointed out that Ki-67as a prognostic marker of intracavitary breast cancer,20% is more reliable than 14% [19,20] . Meta analysis shows that the threshold value of Ki-67 between 5% and 30% [21] .…”

Section: Methodsmentioning

confidence: 99%

The Role of Ki-67 in HR+/HER2- Breast Cancer: a Real-world Study of 956 Patients

Qin

Liu

2022

Preprint

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Purpose: This retrospective study aimed to determine the most suitable cut-off value of Ki-67 expression and further explore the prognostic effect of Ki-67 in hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer;Methods: We assessed the Ki-67 expression of 956 patients with HR+/HER2 breast cancer diagnosed in General Hospital of Ningxia Medical University from 2015 to 2019 by immunohistochemistry, The disease-free survival (DFS) was defined as the time from postoperative to the first local recurrence, distant metastasis or death of the disease. Results: 22.5% was used as the cut-off for low/high Ki-67 expression in HR+/HER2- breast cancer; compared with the commonly used threshold value of Ki-67(14%) in clinic at present, the consistency of the two value is moderate (Kappa = 0.484, P<0.001). The expression of Ki-67 was increased with the increase of grade. (Median: G1:10%; G2:20%; G3:40%. Mean: G1:13%; G2:23%; G3:39%, P<0.001). During the follow-up that 61 patients developed recurrence or metastasis which Ki-67 low expression was found in 21 cases and high expression in 40 cases, the patients with Ki-67 ≥ 22.5% had a 2.937 higher risk of early recurrence and metastasis than the patients with Ki-67< 22.5%, the DFS in patients with high Ki-67 expression was lower than the patients with low Ki-67 expression (96% VS 89%, P<0.05). The common position of distant metastasis were bone, liver and lung, and rare metastases were adrenal gland, bone marrow and pericardium. Recurrence and metastasis mostly occurred in the second and third year after operation, and multi-site metastasis was more common.Conclusions: The cut-off value of Ki-67 expression in HR+/HER2- breast cancer is 22.5%; The patients with Ki-67 ≥ 22.5% had a 2.937 higher risk of early recurrence and metastasis than the patients with Ki-67 < 22.5%.

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The Proper Ki-67 Cut-Off in Hormone Responsive Breast Cancer: A Monoinstitutional Analysis with Long-Term Follow-Up

Cited by 21 publications

References 13 publications

HER2-low breast cancer shows a lower immune response compared to HER2-negative cases

HER2-low breast cancer shows a lower immune response compared to HER2-negative cases

Ductal carcinoma in situ of the male breast: clinical radiological features and management in a cancer referral center

The Role of Ki-67 in HR+/HER2- Breast Cancer: a Real-world Study of 956 Patients

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