Breast Cancer: Two Conclusive Treatment Trials for De-escalation

Chicago, USA – Two clinical trials for de-escalation of breast cancer were presented and highlighted at the annual conference of American Society of Clinical Oncology (ASCO) .

Chemotherapy: no significant benefit in 70 years with high genomic index

The benefit of adjuvant chemotherapy in addition to hormonal therapy remains controversial for patients aged 70 years and older with primary estrogen receptor positive (ER+) and HER2 negative (HER2-) or isolated localized breast cancer.

In this context, the study Aster 70 It is the first multicenter treatment trial based on the analysis of tumor genetic fingerprint, which reflects the risk of relapse, to choose whether or not to have adjuvant chemotherapy in people over 70 years of age.[1]. The aim of the study was to evaluate the contribution of postoperative chemotherapy in addition to hormonal therapy Reverse Hormone therapy alone if the tumor is aggressive (high genomic score).

Dr. Etienne Brin

The results were presented on June 7, 2022 at ASCO by Dr. Etienne Brina medical oncologist, specializing in breast cancer and elderly care at The Curie Institute, who also received the ASCO BJ Kennedy Award for Scientific Excellence in Medical Oncology (see box).

In this prospective trial, the researchers first assessed the genomic tumor grade index (GGI) in all patients. Next, patients with GGI (high risk of relapse) were randomized between chemotherapy plus endocrine therapy versus endocrine therapy alone.

Patients with low GGI did not receive chemotherapy and were followed into the control group.

Doctors chose between 3 chemotherapy regimens: 4 cycles of doxorubicin/cyclophosphamide, unbound doxorubicin/cyclophosphamide, or docetaxel/cyclophosphamide, given every 3 weeks with G-CSF. Hormone therapy consists of a 5-year aromatase inhibitor, tamoxifen, or a tolerance-related sequence.

The primary objective was to demonstrate a survival benefit (OS) associated with chemotherapy in the intent-to-treat population.

Between April 2012 and May 2016, 1969 patients from 61 French and 12 Belgian centers were enrolled in the study. Of these, 1089 (55%) were randomized to one of the two study arms. Median follow-up was 5.8 years at the date of data cutoff (17/12/2021). The median age was 75 years (70-92). Tumors ≥ pT2, pN+, localized relapses were isolated, histological grade III, respectively in 56%, 46%, 11% and 39% of cases.

No significant difference in survival was observed between the two arms (RR 0.85 [0,64-1,13], p = 0.2538). OS at 4 years was 90.5% in the chemotherapy plus endocrine therapy arm and 89.7% in the endocrine therapy alone. The researchers were unable to determine which subgroup had the greatest benefit from chemotherapy.

“This is the first time we have conducted a study of this size in a population that would normally be excluded from clinical trials,” Dr. Breen commented, adding, “Our results raise questions about therapeutic de-escalation in some of our elderly patients. And on the significant bias in our attitudes, and recourse by default. , without being shown, to the same standards as in our younger patients. The amount of information collected in the Aster 70 will allow the study of adjustments and adaptations needed for these treatments, which are often over-prescribed like chemotherapy.”

Aster 70s will allow the study of modifications and adaptations needed for these treatments, which are often over-prescribed, such as chemotherapy.
Dr. Etienne Brin

ASCO BJ Kennedy Geriatric Oncology Award 2022 awarded to Dr. E. Brain

This award rewards a physician for his exceptional contributions to the research, diagnosis, and treatment of cancer in the elderly, and in recognition of his international moving spirit to the subject at both educational and political levels.

“I am very proud of this award given to me today because it is the culmination of many work that has been carried out over several years to care for elderly people with cancer, particularly those with breast cancer. We must continue to develop specific clinical research for this age group of people,” said Dr. Etienne Brin. the elderly”.

Dr Breen is the former Chair of the Breast Cancer Group at EORTC (European Organization for Research and Treatment of Cancer). He chairs the DIALOG Intergroup (GERICO/UCOG) dedicated to the clinical research of elderly patients. He is also the past president of the International Society of Geriatrics and Oncology (SIOG).

“I am delighted with this prestigious transatlantic honor that today honors Dr. Etienne Brin for the work he did for years at Institut Curie,” he noted. Professor Stephen Le Joeldirector of the Curie Institute Hospital Complex in a press release[2].

Can we dispense with conservative radiotherapy after surgery from the age of 55?

Another trial to reduce therapeutic escalation in breast cancer was presented at ASCO, The Trial LuminaThis showed that some patients may be able to avoid radiotherapy after breast-conserving surgery[3].

Adjuvant radiotherapy is usually prescribed after breast-sparing surgery to reduce the risk of recurrence, but treatment is associated with both acute and long-term toxicity.

Women in this trial who did not receive radiotherapy and who were treated with breast-conserving surgery followed by hormone therapy, had an overall survival rate of 97.2%. The local recurrence rate was 2.3%, the primary end point of the study.

Dr.. Timothy Joseph Whelan

“Women 55 years of age and older with low-grade luminal type A breast cancer after breast-conserving surgery and hormone therapy only had a very low rate of local recurrence at 5 years,” said the lead author. Dr.. Timothy Joseph Whelan During his presentation at ASCO [3].

Women 55 years of age or older with low-grade luminal A breast cancer after breast-conserving surgery and treatment with hormone therapy alone had a very low rate of local recurrence at 5 years.
Dr.. Timothy Joseph Whelan

“More than 300,000 [personnes] Invasive breast cancer is diagnosed in North America each year, and the majority are in the United States,” Dr. Whelan said. “We estimate that these findings could apply to 10 to 15% of them, or approximately 30,000 to 40,000 women per year who could avoid the morbidity and cost and the inconvenience of radiotherapy.

Previous studies have shown that in women over the age of 60 with luminal low-grade type A breast cancer who have had breast-conserving surgery only, the local recurrence rate is low. In women over 70, the risk of local recurrence was about 4 to 5%. This new study shows that this option could be considered sooner.

The LUMINA study included patients with luminal type A breast cancer associated with histopathological factors (defined as: ER ≥ 1%, PR > 20%, HER2-negative and Ki67 13.25%).

A prospective, multicenter cohort study included 501 patients aged 55 years and over who had undergone breast-conserving surgery for grade 1-2 T1N0 cancer.

The mean age of patients was 67 years, of whom 442 (88%) were over 75 years old. The mean tumor size was 1.1 cm.

Median follow-up was 5 years. The group was followed every 6 months for the first 2 years and then annually.

At five years, there were 10 local recurrences, a rate of 2.3% (primary end point); Eight breast cancers versus (1.9%), recurrence-free survival rate of 97.3%, disease-free survival rate of 89.9% and overall survival of 97.2% (secondary end points).

“This is a very well-designed and important study,” commented Before Penny R. Anderson (Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia) before adding that this trial was “a significant addition and a very important contribution to the literature demonstrating that breast radiotherapy may not be performed safely in this specific subgroup of breast cancer patients.”

Commenting on the study, he said, Dr. Julie GralowASCO Executive Vice President, said Medscape Medical News “I think there will be a debate about how best to identify this group,” because in this study, patients were screened for Ki67, an indicator of prevalence. However, Ki67 testing is not routinely performed. “Do we need this Ki67 test? Do we need to develop guidelines on how to do this? Is it better than if I had already taken an Oncotype or MammaPrint test to see if a patient needed chemotherapy?”, she asks. “This is where the discussion will be.”

Is it better than if you already had an Oncotype or MammaPrint test to see if a patient needs chemotherapy?
Dr. Julie Gralow

He also commented on the study Dr. Deborah Axelrod (Perlmutter Cancer Center at NYU Langone, NY), praised the prospective and multicenter nature of the LUMINA study while emphasizing some limitations: “Follow-up is 5 years and the local recurrence of ER-positive cancers continues to increase after 5 years, so long-term follow-up will be important “. In addition, she explained that this was a single-arm study, and therefore without a comparison arm.

In practice, she added, patients may prefer a week of partial radiotherapy to the breast, rather than committing to 5 years of hormone therapy as this study does.

Dr. Axelrod concludes: “In general, the take-home message to patients is that bypassing radiotherapy should be considered an option for older women with localized breast cancer with favorable features who are receiving hormone therapy.”

The take-home message for patients is that no radiotherapy should be considered an option for older women with localized breast cancer with favorable features who are receiving hormone therapy.
Dr. Deborah Axelrod

The LUMINA study was sponsored by the Canadian Breast Cancer Foundation and the Canadian Cancer Society. Dr. Whelan reports research funding from Exact Sciences (Inst). Drs Axelrod and Anderson did not report any conflict of interest. Dr. Gralow has reported important links with Genentech, AstraZeneca, Hexal, Puma BioTechnology, Roche, Novartis, Seagen and Genomic Health.

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