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Spotlight on Breast Cancer at Cancer Research Communications and the SABCS

January 12, 2022

The 2021 San Antonio Breast Cancer Symposium (SABCS) took place December 7–10, 2021 and was attended by thousands of participants, both virtually and in person. The SABCS, which has occurred annually since 1977, is jointly sponsored by AACR, the University of Texas Health Science Center, and Baylor College of Medicine. It attracts some of the most groundbreaking clinical and translational science in the breast cancer field each year. The 2021 program was highlighted by new data in the clinical field, including the first demonstration of efficacy of an oral SERD (elacestrant) in the Phase III EMERALD study, new insights into the utility of genomic tests for hormone receptor-positive breast cancer (RxPonder), new data on optimizing antibody-drug conjugates and cargo (deruxtecan versus emtansine), and increasing demonstrations of the potential utility of circulating tumor DNA to guide therapy decisions.

In addition, there were a number of prestigious lectures delivered and awards received by outstanding leaders in the field:

  • Olufunmilayo Olopade, MD, FAACR, received the William L. McGuire Memorial Lecture Award for her work in understanding the genetics of breast cancer in Black women.
  • Helen M. Piwnica-Worms, PhD, received the 2021 AACR Distinguished Lectureship in Breast Cancer Research for her pioneering work in cell cycle regulation and checkpoints.
  • Fabrice André, MD, PhD, received the 2021 AACR Outstanding Investigator Award for Breast Cancer Research for his leadership in key clinical trials that have altered patient care.
  • Carlos Caldas, MD, FMedSci, and Judy E. Garber, MD, MPH, were named recipients of Susan G. Komen Brinker Awards for Distinguished Science for their lifetime achievements in and contributions to the basic and clinical breast cancer fields, respectively.

Cancer Research Communications showcases its inaugural articles in the breast cancer field:

“BRCA1/ATF1-mediated transactivation is involved in resistance to PARP inhibitors and cisplatin”

Endo and Yoshino et al. evaluated the relative activity states of 30 different BRCA1 missense variants using a specialized assay of site-specific homologous recombination (HR) activity (ASHRA). While many of the variants exhibited intermediate phenotypes with residual HR activity, the severely HR-deficient C61G variant—which would normally be predicted to result in sensitivity to PARP inhibitors—was found to promote PARPi resistance through activation of the transcription factor ATF1. These findings suggest that ATF1 may serve as a biomarker for sensitivity to PARPi and platinum-based chemotherapeutics, and that ASHRA is an effective tool to assess HR activity in cancer cells with alterations in BRCA1 or other mediators of HR such as BRCA2 or RAD51.

“Tumor Suppressor PLK2 May Serve as a Biomarker in Triple-Negative Breast Cancer for Improved Response to PLK1 Therapeutics”

Gao et al. demonstrated that polo-like kinase (PLK)2, which is frequently deleted in basal-like and triple-negative breast cancer (TNBC), exerts a tumor suppressive role in breast cancer via its direct interaction with the pro-tumorigenic PLK1. They show that ablation or inhibition of PLK1 is sufficient to mitigate the oncogenic effects of PLK2 loss both in vitro and in vivo, suggesting that PLK2 loss may identify tumors that would respond to the use of PLK1 inhibitors in conjunction with standard-of-care chemotherapy in the clinic.

“Influence of Germline BRCA Genotype on the Survival of Patients with Triple-Negative Breast Cancer”

Villarreal-Garza et al. screened a cohort of Mexican women with early-onset TNBC to determine the effect of various types of BRCA mutations on patient outcomes. They observe that patients with large copy number variations (CNV), such as BRCA1 exon 9-exon 12 deletions, had superior overall survival compared to patients with small indels or point mutations, though recurrence-free survival was not significantly different between the groups. The authors conclude that patients with BRCA pathological variants stemming from large CNV may be less susceptible to BRCA reversion mutations that can cause resistance to therapeutics targeting DNA repair deficiencies.

Q&A with Immuno-oncology Senior Editor, Justin M. Balko:

  • What was the last book you read?
    • The Complete Calvin and Hobbes. It counts. Don't judge.
  • What would you have done if you weren’t in your current occupation?
    • Most definitely a rock star
  • Which scientist (alive or dead) do you admire the most?
    • Galilieo Galilei
  • What do you like to do when you are not working on cancer research?
    • I play guitar, piano, and go for ridiculously long walks
  • Who is your favorite musician?
    • The Mountain Goats, The Counting Crows and The Bleachers
  • What is your favorite food?
    • Most certainly pizza. Or oysters.
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