Julie M. Collins, MD, MPH, an assistant professor at Georgetown University and medical oncologist at MedStar Health, discusses the rationale for CDK4/6 inhibitors in endocrine receptor (ER)–positive breast cancer.

Tumor cell proliferation in many breast cancers is driven by the hyperactivity of the cyclin D–CDK4/6 pathway, says Collins. By blocking this pathway with CDK4/6 inhibitors, the tumor cell proliferation can decrease and prevent these cells from progressing from the G1 phase to S phase of the cell cycle causing cell cycle arrest and a type of cell synesis, according to Collins.

CCND1, which encodes cyclin D, is expressed in high levels in ER-positive breast cancers, adds Collins. CDK4/6 inhibitors have shown strong synergy with antiestrogen therapies, which are used in ER-positive breast cancers. That is the rationale to combine these therapies when treating patients with metastatic ER-positive disease, concludes Collins.

Videos

Julie M. Collins, MD, MPH, discusses the rationale for CDK4/6 inhibitors in endocrine receptor-positive breast cancer.
 

Dr. Collins on the Rationale for CDK4/6 Inhibitors in ER+ Breast Cancer

Experts in breast cancer discuss precision medicine in treatment of patients with metastatic triple negative breast cancer.

Data from the following clinical trials are discussed:

KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. (Cortes J et al. 2020 ASCO annual meeting. Abstract 1000.)

TBCRC 048: A phase II study of olaparib monotherapy in metastatic breast cancer patients with germline or somatic mutations in DNA damage response pathway genes (Olaparib Expanded). (Tung NM et al. 2020 ASCO annual meeting. Abstract 1002.)

Results of a phase II randomized trial of cisplatin +/- veliparib in metastatic triple-negative breast cancer and/or germline 

-associated breast cancer (SWOG S1416). (Sharma P et al. 2020 ASCO annual meeting. Abstract 1001.)

Veliparib plus carboplatin-paclitaxel in patients with HER2-negative advanced/metastatic gBRCA-associated breast cancer: Results in hormone receptor-positive and triple-negative breast cancer subgroups from the phase III BROCADE3 trial. (Ayoub J et al. 2020 ESMO Breast Cancer annual meeting. Abstract 140O.)

Final results of the double-blind placebo-controlled randomized phase II LOTUS trial of first-line ipatasertib + paclitaxel for inoperable locally advanced/metastatic triple-negative breast cancer. (Dent R et al. 2020 ESMO Breast Cancer annual meeting. Abstract 139O.)

Precision Medicine in Metastatic Triple Negative Breast Cancer

KOLs in breast cancer provide insights on de-escalation of adjuvant anti-HER2 therapy and need for HER2 testing of residual disease after neoadjuvant therapy.

Three-year follow-up of neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2-blockade for HER2-positive breast cancer (TRAIN-2): A randomized phase III trial. (van der Voort A et al. 2020 ASCO annual meeting. Abstract 501.)

Primary analysis of KAITLIN: A phase III study of trastuzumab emtansine (T-DM1) + pertuzumab versus trastuzumab + pertuzumab + taxane, after anthracyclines as adjuvant therapy for high-risk HER2-positive early breast cancer. (Harbeck N et al. 2020 ASCO annual meeting. Abstract 500.)

Adjuvant trastuzumab emtansine (T-DM1) vs trastuzumab in patients with residual invasive disease after neoadjuvant therapy for HER2+ breast cancer: Subgroup analysis from KATHERINE. (Loibl S et al. 2020 ESMO Breast Cancer annual meeting. Abstract 96O.)

HER2+ Early-Stage Breast Cancer: Peri-Operative Therapy

Breast cancer experts review recently approved treatment options for relapsed or refractory HER2+ MBC, their intracranial efficacy, and sequencing of therapies.

Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer: HER2CLIMB. (Murthy RK et al. 

Trastuzumab deruxtecan in previously treated HER2-positive breast cancer: DESTINY-Breast01. (Modi S et al. 

Neratinib plus capecitabine versus lapatinib plus capecitabine in HER2+ metastatic breast cancer previously treated with ≥ 2 HER2-directed regimens: phase III NALA trial. (Saura C et al. 

Tucatinib versus placebo added to trastuzumab and capecitabine for patients with previously treated HER2+ metastatic breast cancer with brain metastases: HER2CLIMB. (Lin NU et al. 2020 ASCO annual meeting. Abstract 1005.)

CNS metastases in HER2-positive metastatic breast cancer treated with trastuzumab deruxtecan: DESTINY-Breast01 subgroup analyses. (Jerusalem G et al. 2020 ESMO Breast Cancer annual meeting. Abstract 138O.)

Impact of neratinib on development and progression of central nervous system metastases in patients with HER2-positive metastatic breast cancer: Findings from the NALA, NEfERT-T, and TBCRC 022 trials. (Awada A et al. 2019 SABCS. Poster P2-20-01.)

Trastuzumab deruxtecan vs investigator's choice for HER2-low breast cancer that has spread or cannot be surgically removed: DESTINY-Breast04. (NCT03734029. Updated October 6, 2020. https://clinicaltrials.gov/ct2/show/NCT03734029)

Metastatic HER2+ Breast Cancer

Sarah Sammons, MD, and Julie Collins, MD, discuss the study details of the PARSIFAL and BYLieve trials in patients with metastatic HR+ breast cancer.

PARSIFAL: A randomized, multicenter, open-label, phase II trial to evaluate palbociclib in combination with fulvestrant or letrozole in endocrine-sensitive patients with ER[+]/HER2[-] metastatic breast cancer. (Llombart-Cussac A et al. 2020 ASCO annual meeting. Abstract 1007.)

Alpelisib + fulvestrant in patients with 

-mutated HR+/HER2- advanced breast cancer previously treated with CDK4/6 inhibitor + aromatase inhibitor: BYLieve study results. (Rugo HS et al. 2020 ASCO annual meeting. Abstract 1006.)

Julie Collins, MD, MedStar Georgetown University Hospital

Articles

Dr. Collins on the Rationale for CDK4/6 Inhibitors in ER+ Breast Cancer

Precision Medicine in Metastatic Triple Negative Breast Cancer

HER2+ Early-Stage Breast Cancer: Peri-Operative Therapy

Metastatic HER2+ Breast Cancer

Metastatic HR+ Breast Cancer