Researchers from Dana-Farber Cancer Institute presented more than 30 research studies at the 44th annual San Antonio Breast Cancer Symposium on December 7-10th, 2021. Dana-Farber faculty led and participated in spotlight sessions, debates, posters, lectures, and educational sessions covering both clinical and basic research at this year’s conference. Select presentations by Dana-Farber researchers included:
Antibody-drug conjugate continues to show promise in patients with triple-negative breast cancer
GS1-05 Datopotamab deruxtecan in advanced/metastatic HER2- breast cancer: Results from the phase 1 TROPION-PanTumor01 study
Presenter: Ian Krop, MD, PhD
In a Phase 1 trial, datopotamab deruxtecan, a novel antibody-drug conjugate, continues to demonstrate promising antitumor activity with manageable side effects in patients with previously treated triple-negative breast cancer (TNBC), updated trial results show. Dana-Farber Cancer Institute investigators will present the latest findings of the study, dubbed TROPION-PanTumor01, at the 2021 San Antonio Breast Cancer Symposium.
Of 44 patients with TNBC who received at least one dose of datopotamab deruxtecan in the trial, 34% had their tumors shrink substantially , investigators have found. In the subset of patients who had not previously had treatment with antibody drug conjugates, 52% had tumor responses.
Datopotamab deruxtecan is an antibody-drug conjugate consisting of a monoclonal antibody and a topoisomerase 1 inhibitor – one of a new class of agents aimed to interrupting DNA replication in cancer cells. Preliminary results of the TROPION-PanTumor01 phase 1 trial indicated the conjugate has encouraging antitumor activity in patients with TNBC or non-small cell lung cancer, with a manageable safety profile.
The most common adverse effects of the agent were nausea, mouth sores, hair loss, vomiting, and fatigue, researchers found. While 8 of the patients had their doses reduced because of these or other problems, only 1 patient discontinued treatment as a result of them.
“Patients with TNBC whose cancer has demonstrated resistance to multiple therapies have few treatment options, said Ian Krop MD PhD. “We are therefore very encouraged by the substantial number of patients whose cancer clearly responded to this novel targeted therapy.”
For premenopausal women with breast cancer, ovarian suppression provides greater reduction in long-term risk of recurrence than tamoxifen alone, researchers find
GS2-05. Randomized comparison of adjuvant aromatase inhibitor exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC): update of the combined TEXT and SOFT trials
Presenter: Meredith Regan, ScD
For premenopausal women with hormone receptor-positive (HR+) breast cancer, treatments that suppress ovarian function, combined with tamoxifen or the aromatase inhibitor exemestane, provide persistent reduction in the risk of recurrence compared to tamoxifen alone, long-term results of two large clinical trials shows. The findings, based on a 12.5-year follow-up of patients in the trials, will be presented by Dana-Farber Cancer Institute researchers at the 2021 San Antonio Breast Cancer Symposium.
The two international trials, dubbed SOFT and TEXT, are evaluating post-surgical hormone-blocking therapy in more than 5,700 premenopausal women with early-stage, HR+ breast cancer. Study leaders had previously reported that, at five years of follow-up, ovarian suppression plus tamoxifen reduced the risk of breast cancer recurrence – and appeared to improve survival – more than tamoxifen alone. They also reported that ovarian suppression plus exemestane reduced recurrence to a greater extent than ovarian suppression plus tamoxifen, but without a further improvement in survival.
“The new findings indicate that, at the 12.5-year mark, ovarian suppression plus tamoxifen or exemestane continues to lower the risk of recurrence more than tamoxifen alone for these patients,” says Dana-Farber’s Meredith Regan, ScD, a member of the International Breast Cancer Study Group (IBCSG) that conducted the trials and is analyzing the follow-up data. Investigators also found that the reduction is greatest in patients using exemestane in conjunction with ovarian suppression.
“We continue to see that ovarian suppression reduces the risk of death long-term,” she continues. “In absolute terms, the reductions were more substantial for those at higher clinical risk – on the order of a 10% reduction in death at the 12-year follow-up point. We’re also seeing a later-emerging reduction in death with the use of exemestane and ovarian suppression vs. tamoxifen and ovarian suppression.”
She adds that “long-term follow up of these young women is quite important because of a continued risk of having a recurrence of their breast cancer even after 10 years. The IBCSG plans five more years of follow-up with these women.”
Patient involvement driving success of Metastatic Breast Cancer Project
OT1-19-01 The metastatic breast cancer project: Generating the clinical and genomic landscape of metastatic breast cancer through patient-partnered research
Presenter: Nikhil Wagle, MD
A groundbreaking project that engages patients in an effort to build a clinical and genomic dataset for research in metastatic breast cancer has prompted thousands of patients to participate by sharing their tissue samples, information, and experiences, project leaders at Dana-Farber Cancer Institute reported at the 2021 San Antonio Breast Cancer Symposium.
The Metastatic Breast Cancer Project has reached out to patients through social media, advocacy groups, and a website by which they can join. Since the project’s launch in 2015, well over 6,000 patients with metastatic breast cancer have registered. Registrants receive an online consent form that asks for permission to obtain and analyze their medical records and samples. Consented patients receive a kit with which they mail back a saliva sample, which is used to extract germline DNA, and/or a blood sample, which is used to extract germline DNA and cell-free DNA. Participants’ medical providers are contacted for medical records and a portion of stored tumor biopsies.
As of June 2021, 3,456 patients receiving care at over 1,700 institutions have consented to share medical records and tumor/saliva/blood samples and to have genomic analysis performed. To date, patient data has been cited in over 40 publications. Study updates are shared with participants regularly.
The project continues to enroll new patients, generate additional data, and perform integrated clinical and genomic analyses with the goal of building a dataset that is representative of patients with MBC. Several community engagement efforts are underway to more directly reach patients in underrepresented communities, including partnerships with faith-based organizations and colleges/universities, as well as targeted engagement with the African American and Spanish-language communities. The resulting publicly shared, clinically annotated dataset allows researchers to identify patients with specific phenotypes, who have often been challenging to identify with traditional approaches.
Aromatase inhibitors reduce risk of cancer recurrence in women with ER+ breast cancer treated with ovarian suppression, study finds
GS2-04. Aromatase inhibitors versus tamoxifen in pre-menopausal women with estrogen receptor positive early stage breast cancer treated with ovarian suppression: A patient level meta-analysis of 7,030 women in four randomised trials
Presenter: Meredith Regan, ScD
In premenopausal women with estrogen receptor-positive (ER+) breast cancer who are receiving therapy to suppress the production of estrogen by the ovaries, the risk of cancer recurrence is about 20% lower when treated with aromatase inhibitor drugs than with tamoxifen, a review of data from four large clinical trials indicates.
The findings, point to the need for longer follow-up to determine whether the use of aromatase inhibitors in patients undergoing ovarian suppression impacts long-term breast cancer mortality, say the study authors – members of an international collaboration including researchers at Dana-Farber Cancer Institute.
Aromatase inhibitors, which prevent androgen and other hormones from being converted into tumor-fueling estrogen, lower the risk of dying from breast cancer in postmenopausal women. They aren’t effective in premenopausal women, however, largely because the ovaries compensate for the drop in estrogen levels by producing more of the hormone.
“In premenopausal women, this compensatory response can be overcome by medically induced ovarian suppression or removal. This suggested that aromatase inhibitors may also be more effective than tamoxifen at preventing breast cancer recurrence when these patients were receiving ovarian suppression. In this study, we sought to estimate the magnitude of this benefit,” says Dana-Farber’s Meredith Regan, ScD, the senior author of The Lancet Oncology paper.
Regan and her colleagues analyzed data from four clinical trials that included 7,030 premenopausal women with ER+ breast cancer treated with ovarian suppression or removal. They compared outcomes of patients treated with tamoxifen to those of patients treated with aromatase inhibitors for three to five years after an average follow-up of eight years.
“We found the rate of cancer recurrence averaged 21% lower for the women who received aromatase inhibitors,” Regan states. “Over the first five years, the risk was reduced from 10.1% to 6.9% of patients experiencing recurrence.” The reduction was greater for patients whose tumors were also HER2-negative than those whose tumors were HER2-positive.
Use of aromatase inhibitors did result in more bone fractures, similar to what had been seen in postmenopausal women.
