Effect of internal subtype on the efficacy of CDK4/6 inhibitor therapy in advanced HR+/HER2breast cancer: A review

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Abstract

The classification of breast cancer (BC) by immunohistochemical phenotypes is widely used in routine clinical practice. However, the genetic profile of the tumor does not always correspond to the pathomorphological one, which can significantly affect the prognosis and predict the effectiveness of therapy in BC. This literature review examines the effectiveness of endocrine therapy depending on the internal subtype of BC, and also presents data on the effectiveness of CDK4/6 inhibitors in these subgroups. It has been shown that during metastasis, the tumor acquires a more aggressive subtype (for example, it switches from luminal to HER2-E or basal-like), which can be stopped when using CDK4/6 inhibitors: the change of the internal subtype passes into a more favorable group.

About the authors

Katerina S. Grechukhina

Loginov Moscow Clinical Scientific Center

Author for correspondence.
Email: dr.grechukhina@gmail.com
ORCID iD: 0000-0002-0616-5477

Cand. Sci. (Med.)

Russian Federation, Moscow

Daria A. Filonenko

Loginov Moscow Clinical Scientific Center

Email: dr.grechukhina@gmail.com
ORCID iD: 0000-0002-7224-3111

Cand. Sci. (Med.)

Russian Federation, Moscow

Margarita V. Sukhova

Loginov Moscow Clinical Scientific Center

Email: dr.grechukhina@gmail.com
ORCID iD: 0009-0004-7119-0160

oncologist

Russian Federation, Moscow

Liudmila G. Zhukova

Loginov Moscow Clinical Scientific Center

Email: dr.grechukhina@gmail.com
ORCID iD: 0000-0003-4848-6938

D. Sci. (Med.), Corr. Memb. RAS

Russian Federation, Moscow

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Supplementary files

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2. Fig. 1. Schematic representation of the correlation between morphologic phenotype and internal subtype of breast cancer (BC).

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3. Fig. 2. Baseline Ki-67 values and Ki-67 values at the time of surgery in patients with luminal A and B, HER2-E subtypes of BC [27].

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4. Fig. 3. PFS differences according to internal subtype: a – in the PALOMA-2 and PALOMA-3 studies; b – in the pooled MONALEESA analysis [3, 6, 36].

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5. Fig. 4. Distribution of HR+/HER2- samples by internal subtypes in the MONALEESA study cycle (from left to right: -2, -3, -7, pooled analysis), % [3].

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6. Fig. 5. Median PFS according to internal subtype of BC in the pooled analysis of the MONALEESA trials: a – placebo group; b – ribociclib group.

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7. Fig. 6. Overall response rate according to internal subtype of BC in the pooled analysis of the MONALEESA trials.

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8. Fig. 7. Median overall survival (post-hoc analysis) according to internal BC subtype in the pooled analysis of the MONALEESA trials: a – in the placebo group; b – in the ribociclib group [37, 39].

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9. Fig. 8. Median PFS and overall response rate with therapy with palbociclib/abemaciclib and ribociclib for: a – luminal A; b – luminal B; c – HER2-E subtypes.

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10. Fig. 9. Change in internal tumor subtype during metastasis according to studies, %: a – J. Cejalvo et al.; b – S. Jørgensen et al. [2, 42].

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11. Fig. 10. Schematic representation of the effect of ribociclib on changing tumor biology. Ribociclib probably induces a switch to a less aggressive luminal subtype [30].

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