Lead author Roisin Connolly, M.B.B.Ch., M.D., associate professor of oncology at the Kimmel Cancer Center, said the change in sugar uptake on PET scans from baseline to two weeks after starting treatment, and the value at the two-week time point itself, had the best ability to predict response to HER2-directed therapy with high sensitivity and very high negative predictive value. High sugar levels two weeks after treatment, says Connolly, indicate the tumor likely will not fully respond to antibodies alone and will need chemotherapy.

She said there is great interest at this time in "de-escalation" of treatment strategies in breast cancer, which aim to minimize toxicity while maintaining the efficacy.


"Based on our findings, if the sugar uptake shown on the scans is below a certain level at two weeks, antibody therapy may be enough to induce a complete response, and those patients may be spared the toxic e?ects of chemotherapy."

ER-negative, HER2-positive breast cancer accounts for about 8 percent of all breast cancers. Standard treatment calls for a combination approach of surgery to remove the bulk of the tumor, and a combination of antibody therapy to cut o? the ability of the HER2 gene to support the growth of breast cancer cells and chemotherapy to directly kill the cancer cells.

"So in the future, we may be able to offer this as a chemo-free approach. Further research is still required to investigate this before it can become standard practice in the clinic to make treatment decisions, but it is extremely promising," Connolly says.

The 88 women enrolled in the study were treated between January 2014 and August 2017, and 83 were evaluated for the primary study. All four cycles of targeted therapy drugs were completed in 85 percent of cases (75/88), and all 83 patients who completed follow-up had surgery after the therapy.


In addition to Connolly and Stearns, other study authors included Jeffrey Leal, Lilja Solnes, Chiung-Yu- Huang, Ashley Carpenter, Katy Gaffney, Vandana Abramson, Lisa Carey, Minetta Liu, Mothaffar Rimawi, Jennifer Specht, Anna Maria Storniolo, Vicente Valero, Christos Vaklavas, Ian Krop, Eric Winer, Melissa Camp, Robert Miller, Antonio Wolff, Ashley Cimino-Mathews, Ben Park and Richard Wahl.

The research was supported by TBCRC and its foundation partners (The AVON Foundation, The Breast Cancer Research Foundation and Susan G. Komen for the Cure), an SKCCC Core Grant (P30-CA006973), an NCI Quantitative Imaging Network contract (5U01CA140204) and Genentech Inc., including supply of pertuzumab and trastuzumab. Grant funding was obtained from the American Society of Clinical Oncology Conquer Cancer Foundation Career Development Award (2013) and the AVON Center of Excellence.

COI: Connolly has received research grants to institution from Novartis, Puma Biotechnology, Merck, Merrimack, Genentech and Macrogenics. Solnes has received research grants to institution from Progenics and Endocyte. Wolff has received research grants to institution from Myriad Genetics and Pfizer, is named inventor on one or more issued patents or pending patent applications relating to methylation in breast cancer, has assigned his rights to The Johns Hopkins University and participates in a royalty sharing agreement with the university. Cimino-Mathews has received research funding from Bristol-Myers Squibb. Park has stock and a consulting role with Loxo Oncology Inc.; a consulting role with compensation to his institution from Foundation Medicine, Casdin Capital, H3 Biomedicine, Roche and Lilly; speakers' bureau to disclose with Astra Zeneca; research funding to institution from Foundation Medicine Inc., Bristol Myers Squibb and Biocept; and patents or intellectual property to institution from Horizon Discovery, LTD. Stearns has received research grants to institution from Abbvie, Biocept, Pfizer, Novartis, Medimmune and Puma Biotechnology, and served as a consultant to Iridium Therapeutics, Inc.

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