Breast Cancer ICYMI

Key clinical point: Home-based exercise and nutritional intervention vs usual care (UC) routine improved the physical activity levels, diet quality, and pathological complete response (pCR) rates in patients who initiated chemotherapy after a breast cancer (BC) diagnosis.

Major finding: Women in the intervention vs UC group reported greater improvements in physical activity (143.4 vs 47.7 minutes/week; P < .001) and a higher intake of fruits, vegetables, and dietary fiber (P ≤ .01) along with increased pCR rates (53% vs 28%; P  =  .037).

Study details: Findings are from the Lifestyle, Exercise, and Nutrition Early After Breast Cancer study including 173 women with newly diagnosed stages I-III breast cancer who initiated chemotherapy and were randomly assigned to undergo either a UC routine or a home-based exercise and nutritional intervention.

Disclosures: This study was financially supported by the corresponding author ML Irwin. Some authors declared serving in the speakers’ bureau of or in consulting, advisory, or leadership roles in or receiving honoraria from various sources.

Source: Sanft T et al. Randomized trial of exercise and nutrition on chemotherapy completion and pathologic complete response in women with breast cancer: The Lifestyle, Exercise, and Nutrition Early After Diagnosis study. J Clin Oncol. 2023 (Sep 1). doi: 10.1200/JCO.23.00871

Key clinical point: Home-based exercise and nutritional intervention vs usual care (UC) routine improved the physical activity levels, diet quality, and pathological complete response (pCR) rates in patients who initiated chemotherapy after a breast cancer (BC) diagnosis.

Major finding: Women in the intervention vs UC group reported greater improvements in physical activity (143.4 vs 47.7 minutes/week; P < .001) and a higher intake of fruits, vegetables, and dietary fiber (P ≤ .01) along with increased pCR rates (53% vs 28%; P  =  .037).

Study details: Findings are from the Lifestyle, Exercise, and Nutrition Early After Breast Cancer study including 173 women with newly diagnosed stages I-III breast cancer who initiated chemotherapy and were randomly assigned to undergo either a UC routine or a home-based exercise and nutritional intervention.

Disclosures: This study was financially supported by the corresponding author ML Irwin. Some authors declared serving in the speakers’ bureau of or in consulting, advisory, or leadership roles in or receiving honoraria from various sources.

Source: Sanft T et al. Randomized trial of exercise and nutrition on chemotherapy completion and pathologic complete response in women with breast cancer: The Lifestyle, Exercise, and Nutrition Early After Diagnosis study. J Clin Oncol. 2023 (Sep 1). doi: 10.1200/JCO.23.00871

Key clinical point: Home-based exercise and nutritional intervention vs usual care (UC) routine improved the physical activity levels, diet quality, and pathological complete response (pCR) rates in patients who initiated chemotherapy after a breast cancer (BC) diagnosis.

Major finding: Women in the intervention vs UC group reported greater improvements in physical activity (143.4 vs 47.7 minutes/week; P < .001) and a higher intake of fruits, vegetables, and dietary fiber (P ≤ .01) along with increased pCR rates (53% vs 28%; P  =  .037).

Study details: Findings are from the Lifestyle, Exercise, and Nutrition Early After Breast Cancer study including 173 women with newly diagnosed stages I-III breast cancer who initiated chemotherapy and were randomly assigned to undergo either a UC routine or a home-based exercise and nutritional intervention.

Disclosures: This study was financially supported by the corresponding author ML Irwin. Some authors declared serving in the speakers’ bureau of or in consulting, advisory, or leadership roles in or receiving honoraria from various sources.

Source: Sanft T et al. Randomized trial of exercise and nutrition on chemotherapy completion and pathologic complete response in women with breast cancer: The Lifestyle, Exercise, and Nutrition Early After Diagnosis study. J Clin Oncol. 2023 (Sep 1). doi: 10.1200/JCO.23.00871

Key clinical point: Pyrotinib led to promising long-term outcomes and was well-tolerated in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (BC) and brain metastases (BM).

Major finding: In patients with BM, the overall median progression-free survival (PFS), considering both intracranial and extracranial lesions, was 7.50 months (95% CI 5.84-9.16) and median overall survival was 21.27 months (95% CI 20.10-22.44), with the median PFS not improving in patients who received vs did not receive radiotherapy (P  =  .319). Diarrhea (any grade) was the most common adverse event.

Study details: This real-world study included 239 patients with HER2+ metastatic BC who received pyrotinib-based therapy, of whom 61 patients had BM.

Disclosures: This study was supported by the keyAtlas precision medicine and clinical research project of Shanghai Science & Technology Development Foundation, China. The authors declared no conflicts of interest.

Source: Liang X et al. Long-term outcome analysis of pyrotinib in patients with HER2-Positive metastatic breast cancer and brain metastasis: A real-world study. Oncologist. 2023 (Aug 17). doi: 10.1093/oncolo/oyad228

Key clinical point: Pyrotinib led to promising long-term outcomes and was well-tolerated in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (BC) and brain metastases (BM).

Major finding: In patients with BM, the overall median progression-free survival (PFS), considering both intracranial and extracranial lesions, was 7.50 months (95% CI 5.84-9.16) and median overall survival was 21.27 months (95% CI 20.10-22.44), with the median PFS not improving in patients who received vs did not receive radiotherapy (P  =  .319). Diarrhea (any grade) was the most common adverse event.

Study details: This real-world study included 239 patients with HER2+ metastatic BC who received pyrotinib-based therapy, of whom 61 patients had BM.

Disclosures: This study was supported by the keyAtlas precision medicine and clinical research project of Shanghai Science & Technology Development Foundation, China. The authors declared no conflicts of interest.

Source: Liang X et al. Long-term outcome analysis of pyrotinib in patients with HER2-Positive metastatic breast cancer and brain metastasis: A real-world study. Oncologist. 2023 (Aug 17). doi: 10.1093/oncolo/oyad228

Key clinical point: Pyrotinib led to promising long-term outcomes and was well-tolerated in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (BC) and brain metastases (BM).

Major finding: In patients with BM, the overall median progression-free survival (PFS), considering both intracranial and extracranial lesions, was 7.50 months (95% CI 5.84-9.16) and median overall survival was 21.27 months (95% CI 20.10-22.44), with the median PFS not improving in patients who received vs did not receive radiotherapy (P  =  .319). Diarrhea (any grade) was the most common adverse event.

Study details: This real-world study included 239 patients with HER2+ metastatic BC who received pyrotinib-based therapy, of whom 61 patients had BM.

Disclosures: This study was supported by the keyAtlas precision medicine and clinical research project of Shanghai Science & Technology Development Foundation, China. The authors declared no conflicts of interest.

Source: Liang X et al. Long-term outcome analysis of pyrotinib in patients with HER2-Positive metastatic breast cancer and brain metastasis: A real-world study. Oncologist. 2023 (Aug 17). doi: 10.1093/oncolo/oyad228

Key clinical point: Adjuvant capecitabine plus ibandronate failed to show improved survival outcomes compared with ibandronate alone in older patients with node-positive/high-risk node-negative breast cancer (BC).

Major finding: At a median follow-up of 61 months, the 5-year invasive disease-free survival rates were comparable between the adjuvant ibandronate + capecitabine and ibandronate arms (hazard ratio 0.96; 95% CI 0.78-1.19). The incidences of high-grade gastrointestinal disorders (6.7% vs 1.0%; P < .001) and skin toxicity (14.6% vs 0.6%; P < .01) were significantly higher in the ibandronate + capecitabine vs ibandronate arm.

Study details: Findings are from a phase 3 study including 1358 patients age ≥ 65 years with early BC who were randomly assigned to receive ibandronate with or without capecitabine.

Disclosures: This study was sponsored by the German Breast Group. Some authors declared receiving personal fees, grants, contracts, consulting fees, payment, honoraria, support for attending meetings, or travel support from or having other ties with various sources.

Source: Schmidt M et al. Adjuvant capecitabine versus nihil in older patients with node-positive/high-risk node-negative early breast cancer receiving ibandronate - The ICE Randomized Clinical Trial. Eur J Cancer. 2023;113324 (Sep 6). doi: 10.1016/j.ejca.2023.113324

Key clinical point: Adjuvant capecitabine plus ibandronate failed to show improved survival outcomes compared with ibandronate alone in older patients with node-positive/high-risk node-negative breast cancer (BC).

Major finding: At a median follow-up of 61 months, the 5-year invasive disease-free survival rates were comparable between the adjuvant ibandronate + capecitabine and ibandronate arms (hazard ratio 0.96; 95% CI 0.78-1.19). The incidences of high-grade gastrointestinal disorders (6.7% vs 1.0%; P < .001) and skin toxicity (14.6% vs 0.6%; P < .01) were significantly higher in the ibandronate + capecitabine vs ibandronate arm.

Study details: Findings are from a phase 3 study including 1358 patients age ≥ 65 years with early BC who were randomly assigned to receive ibandronate with or without capecitabine.

Disclosures: This study was sponsored by the German Breast Group. Some authors declared receiving personal fees, grants, contracts, consulting fees, payment, honoraria, support for attending meetings, or travel support from or having other ties with various sources.

Source: Schmidt M et al. Adjuvant capecitabine versus nihil in older patients with node-positive/high-risk node-negative early breast cancer receiving ibandronate - The ICE Randomized Clinical Trial. Eur J Cancer. 2023;113324 (Sep 6). doi: 10.1016/j.ejca.2023.113324

Key clinical point: Adjuvant capecitabine plus ibandronate failed to show improved survival outcomes compared with ibandronate alone in older patients with node-positive/high-risk node-negative breast cancer (BC).

Major finding: At a median follow-up of 61 months, the 5-year invasive disease-free survival rates were comparable between the adjuvant ibandronate + capecitabine and ibandronate arms (hazard ratio 0.96; 95% CI 0.78-1.19). The incidences of high-grade gastrointestinal disorders (6.7% vs 1.0%; P < .001) and skin toxicity (14.6% vs 0.6%; P < .01) were significantly higher in the ibandronate + capecitabine vs ibandronate arm.

Study details: Findings are from a phase 3 study including 1358 patients age ≥ 65 years with early BC who were randomly assigned to receive ibandronate with or without capecitabine.

Disclosures: This study was sponsored by the German Breast Group. Some authors declared receiving personal fees, grants, contracts, consulting fees, payment, honoraria, support for attending meetings, or travel support from or having other ties with various sources.

Source: Schmidt M et al. Adjuvant capecitabine versus nihil in older patients with node-positive/high-risk node-negative early breast cancer receiving ibandronate - The ICE Randomized Clinical Trial. Eur J Cancer. 2023;113324 (Sep 6). doi: 10.1016/j.ejca.2023.113324

Key clinical point: Adding ovarian function suppression (OFS) to adjuvant tamoxifen for 2 years demonstrated consistent improvement in disease-free survival (DFS) outcomes and high overall survival (OS) rates in women with estrogen receptor-positive (ER+) breast cancer (BC) who remained premenopausal or regained ovarian function after chemotherapy.

Major finding: The 8-year DFS rates improved consistently in women who received tamoxifen + OFS vs tamoxifen only (85.4% vs 80.2%; hazard ratio 0.67; P  =  .003). Although the 8-year OS rates were comparable between both treatment groups (P  =  .305), they were considerably high (>95%).

Study details: Findings are from an 8-year follow-up of the phase 3 ASTRRA trial including 1282 premenopausal women with ER+ BC, who remained premenopausal or regained ovarian function after chemotherapy and were randomly assigned to receive tamoxifen with or without OFS.

Disclosures: This study was supported by the Korea Health Industry Development Institute, Republic of Korea. Some authors declared receiving honoraria or research funding from or serving in consulting or advisory roles with various sources.

Source: Baek SY et al. Adding ovarian suppression to tamoxifen for premenopausal women with hormone receptor-positive breast cancer after chemotherapy: An 8-year follow-up of the ASTRRA trial. J Clin Oncol. 2023 (Aug 22). doi: 10.1200/JCO.23.00557

Key clinical point: Adding ovarian function suppression (OFS) to adjuvant tamoxifen for 2 years demonstrated consistent improvement in disease-free survival (DFS) outcomes and high overall survival (OS) rates in women with estrogen receptor-positive (ER+) breast cancer (BC) who remained premenopausal or regained ovarian function after chemotherapy.

Major finding: The 8-year DFS rates improved consistently in women who received tamoxifen + OFS vs tamoxifen only (85.4% vs 80.2%; hazard ratio 0.67; P  =  .003). Although the 8-year OS rates were comparable between both treatment groups (P  =  .305), they were considerably high (>95%).

Study details: Findings are from an 8-year follow-up of the phase 3 ASTRRA trial including 1282 premenopausal women with ER+ BC, who remained premenopausal or regained ovarian function after chemotherapy and were randomly assigned to receive tamoxifen with or without OFS.

Disclosures: This study was supported by the Korea Health Industry Development Institute, Republic of Korea. Some authors declared receiving honoraria or research funding from or serving in consulting or advisory roles with various sources.

Source: Baek SY et al. Adding ovarian suppression to tamoxifen for premenopausal women with hormone receptor-positive breast cancer after chemotherapy: An 8-year follow-up of the ASTRRA trial. J Clin Oncol. 2023 (Aug 22). doi: 10.1200/JCO.23.00557

Key clinical point: Adding ovarian function suppression (OFS) to adjuvant tamoxifen for 2 years demonstrated consistent improvement in disease-free survival (DFS) outcomes and high overall survival (OS) rates in women with estrogen receptor-positive (ER+) breast cancer (BC) who remained premenopausal or regained ovarian function after chemotherapy.

Major finding: The 8-year DFS rates improved consistently in women who received tamoxifen + OFS vs tamoxifen only (85.4% vs 80.2%; hazard ratio 0.67; P  =  .003). Although the 8-year OS rates were comparable between both treatment groups (P  =  .305), they were considerably high (>95%).

Study details: Findings are from an 8-year follow-up of the phase 3 ASTRRA trial including 1282 premenopausal women with ER+ BC, who remained premenopausal or regained ovarian function after chemotherapy and were randomly assigned to receive tamoxifen with or without OFS.

Disclosures: This study was supported by the Korea Health Industry Development Institute, Republic of Korea. Some authors declared receiving honoraria or research funding from or serving in consulting or advisory roles with various sources.

Source: Baek SY et al. Adding ovarian suppression to tamoxifen for premenopausal women with hormone receptor-positive breast cancer after chemotherapy: An 8-year follow-up of the ASTRRA trial. J Clin Oncol. 2023 (Aug 22). doi: 10.1200/JCO.23.00557

Key clinical point: In patients with human epidermal growth factor receptor 2-positive (ERBB2+, aka HER2+) metastatic breast cancer (BC), anti-ERBB2 treatment without vs with chemotherapy worsened the progression-free survival (PFS) rate but did not yield detrimental overall survival (OS) outcomes.

Major finding: Patients who did not receive vs received chemotherapy showed comparable OS rates at 2 years (79.0%; 90% CI 71.4%-85.4% vs 78.1%; 90% CI 70.4%-84.5%) but had shorter median PFS (8.4 months; 95% CI 7.9-12.0 vs 23.3 months; 95% CI 18.9-33.1).

Study details: This secondary analysis of a phase 2 trial included 210 patients with ERBB2+ metastatic BC who were randomly assigned to receive pertuzumab + trastuzumab with or without chemotherapy followed by trastuzumab-emtansine as the second-line therapy in both groups.

Disclosures: This study was supported by F. Hoffmann-La Roche AG and other sources. B Thürlimann declared owning stocks from F. Hoffmann-La Roche AG and some other authors declared ties with various sources, including F. Hoffmann-La Roche AG.

Source: Huober J et al for the Swiss Group for Clinical Cancer Research, Unicancer Breast Group, and Dutch Breast Cancer Research Group. Pertuzumab plus trastuzumab with or without chemotherapy followed by emtansine in ERBB2-positive metastatic breast cancer: A secondary analysis of a randomized clinical trial. JAMA Oncol. 2023 (Aug 10). doi: 10.1001/jamaoncol.2023.2909

Key clinical point: In patients with human epidermal growth factor receptor 2-positive (ERBB2+, aka HER2+) metastatic breast cancer (BC), anti-ERBB2 treatment without vs with chemotherapy worsened the progression-free survival (PFS) rate but did not yield detrimental overall survival (OS) outcomes.

Major finding: Patients who did not receive vs received chemotherapy showed comparable OS rates at 2 years (79.0%; 90% CI 71.4%-85.4% vs 78.1%; 90% CI 70.4%-84.5%) but had shorter median PFS (8.4 months; 95% CI 7.9-12.0 vs 23.3 months; 95% CI 18.9-33.1).

Study details: This secondary analysis of a phase 2 trial included 210 patients with ERBB2+ metastatic BC who were randomly assigned to receive pertuzumab + trastuzumab with or without chemotherapy followed by trastuzumab-emtansine as the second-line therapy in both groups.

Disclosures: This study was supported by F. Hoffmann-La Roche AG and other sources. B Thürlimann declared owning stocks from F. Hoffmann-La Roche AG and some other authors declared ties with various sources, including F. Hoffmann-La Roche AG.

Source: Huober J et al for the Swiss Group for Clinical Cancer Research, Unicancer Breast Group, and Dutch Breast Cancer Research Group. Pertuzumab plus trastuzumab with or without chemotherapy followed by emtansine in ERBB2-positive metastatic breast cancer: A secondary analysis of a randomized clinical trial. JAMA Oncol. 2023 (Aug 10). doi: 10.1001/jamaoncol.2023.2909

Key clinical point: In patients with human epidermal growth factor receptor 2-positive (ERBB2+, aka HER2+) metastatic breast cancer (BC), anti-ERBB2 treatment without vs with chemotherapy worsened the progression-free survival (PFS) rate but did not yield detrimental overall survival (OS) outcomes.

Major finding: Patients who did not receive vs received chemotherapy showed comparable OS rates at 2 years (79.0%; 90% CI 71.4%-85.4% vs 78.1%; 90% CI 70.4%-84.5%) but had shorter median PFS (8.4 months; 95% CI 7.9-12.0 vs 23.3 months; 95% CI 18.9-33.1).

Study details: This secondary analysis of a phase 2 trial included 210 patients with ERBB2+ metastatic BC who were randomly assigned to receive pertuzumab + trastuzumab with or without chemotherapy followed by trastuzumab-emtansine as the second-line therapy in both groups.

Disclosures: This study was supported by F. Hoffmann-La Roche AG and other sources. B Thürlimann declared owning stocks from F. Hoffmann-La Roche AG and some other authors declared ties with various sources, including F. Hoffmann-La Roche AG.

Source: Huober J et al for the Swiss Group for Clinical Cancer Research, Unicancer Breast Group, and Dutch Breast Cancer Research Group. Pertuzumab plus trastuzumab with or without chemotherapy followed by emtansine in ERBB2-positive metastatic breast cancer: A secondary analysis of a randomized clinical trial. JAMA Oncol. 2023 (Aug 10). doi: 10.1001/jamaoncol.2023.2909

Key clinical point: Sacituzumab govitecan outperformed chemotherapy in terms of overall survival outcomes and showed a manageable safety profile in patients with pretreated, endocrine-resistant hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2–) metastatic breast cancer (BC) who had limited treatment options.

Major finding: Sacituzumab govitecan vs chemotherapy improved overall survival by 3.2 months (hazard ratio 0.79; P  =  .020). No new adverse events (AE) were reported; however, 1 fatal AE (septic shock caused by neutropenic colitis) was determined to be related to sacituzumab govitecan treatment.

Study details: Findings are from the phase 3 TROPiCS-02 study including 543 patients with pretreated, endocrine-resistant HR+/HER2− metastatic BC who were randomly assigned to receive either sacituzumab govitecan or single-agent chemotherapy of physician’s choice.

Disclosures: This study was funded by Gilead Sciences. Six authors declared being current or former employees of and owning stocks in Gilead Sciences, and several other authors declared ties with various sources, including Gilead Sciences.

Source: Rugo HS et al. Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): A randomised, open-label, multicentre, phase 3 trial. Lancet. 2023 (Aug 23). doi: 10.1016/S0140-6736(23)01245-X

Key clinical point: Sacituzumab govitecan outperformed chemotherapy in terms of overall survival outcomes and showed a manageable safety profile in patients with pretreated, endocrine-resistant hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2–) metastatic breast cancer (BC) who had limited treatment options.

Major finding: Sacituzumab govitecan vs chemotherapy improved overall survival by 3.2 months (hazard ratio 0.79; P  =  .020). No new adverse events (AE) were reported; however, 1 fatal AE (septic shock caused by neutropenic colitis) was determined to be related to sacituzumab govitecan treatment.

Study details: Findings are from the phase 3 TROPiCS-02 study including 543 patients with pretreated, endocrine-resistant HR+/HER2− metastatic BC who were randomly assigned to receive either sacituzumab govitecan or single-agent chemotherapy of physician’s choice.

Disclosures: This study was funded by Gilead Sciences. Six authors declared being current or former employees of and owning stocks in Gilead Sciences, and several other authors declared ties with various sources, including Gilead Sciences.

Source: Rugo HS et al. Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): A randomised, open-label, multicentre, phase 3 trial. Lancet. 2023 (Aug 23). doi: 10.1016/S0140-6736(23)01245-X

Key clinical point: Sacituzumab govitecan outperformed chemotherapy in terms of overall survival outcomes and showed a manageable safety profile in patients with pretreated, endocrine-resistant hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2–) metastatic breast cancer (BC) who had limited treatment options.

Major finding: Sacituzumab govitecan vs chemotherapy improved overall survival by 3.2 months (hazard ratio 0.79; P  =  .020). No new adverse events (AE) were reported; however, 1 fatal AE (septic shock caused by neutropenic colitis) was determined to be related to sacituzumab govitecan treatment.

Study details: Findings are from the phase 3 TROPiCS-02 study including 543 patients with pretreated, endocrine-resistant HR+/HER2− metastatic BC who were randomly assigned to receive either sacituzumab govitecan or single-agent chemotherapy of physician’s choice.

Disclosures: This study was funded by Gilead Sciences. Six authors declared being current or former employees of and owning stocks in Gilead Sciences, and several other authors declared ties with various sources, including Gilead Sciences.

Source: Rugo HS et al. Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): A randomised, open-label, multicentre, phase 3 trial. Lancet. 2023 (Aug 23). doi: 10.1016/S0140-6736(23)01245-X

Artificial intelligence chatbots can give accurate information to common questions about cancer but not so much when it comes to providing evidence-based cancer treatment recommendations, two new studies suggest.

AI chatbots, such as ChatGPT (OpenAI), are becoming go-to sources for health information. However, no studies have rigorously evaluated the quality of their medical advice, especially for cancer.

Two new studies published in JAMA Oncology did just that.

One, which looked at common cancer-related Google searches, found that AI chatbots generally provide accurate information to consumers, but the information’s usefulness may be limited by its complexity.

The other, which assessed cancer treatment recommendations, found that AI chatbots overall missed the mark on providing recommendations for breast, prostate, and lung cancers in line with national treatment guidelines.

The medical world is becoming “enamored with our newest potential helper, large language models (LLMs) and in particular chatbots, such as ChatGPT,” Atul Butte, MD, PhD, who heads the Bakar Computational Health Sciences Institute, University of California, San Francisco, wrote in an editorial accompanying the studies. “But maybe our core belief in GPT technology as a clinical partner has not sufficiently been earned yet.”

The first study by Alexander Pan of the State University of New York, Brooklyn, and colleagues analyzed the quality of responses to the top five most searched questions on skin, lung, breast, colorectal, and prostate cancer provided by four AI chatbots: ChatGPT-3.5, Perplexity (Perplexity.AI), Chatsonic (Writesonic), and Bing AI (Microsoft).

Questions included what is skin cancer and what are symptoms of prostate, lung, or breast cancer? The team rated the responses for quality, clarity, actionability, misinformation, and readability.

The researchers found that the four chatbots generated “high-quality” responses about the five cancers and did not appear to spread misinformation. Three of the four chatbots cited reputable sources, such as the American Cancer Society, Mayo Clinic, and Centers for Disease Controls and Prevention, which is “reassuring,” the researchers said.

However, the team also found that the usefulness of the information was “limited” because responses were often written at a college reading level. Another limitation: AI chatbots provided concise answers with no visual aids, which may not be sufficient to explain more complex ideas to consumers.

“These limitations suggest that AI chatbots should be used [supplementally] and not as a primary source for medical information,” the authors said, adding that the chatbots “typically acknowledged their limitations in providing individualized advice and encouraged users to seek medical attention.”

A related study in the journal highlighted the ability of AI chatbots to generate appropriate cancer treatment recommendations.

In this analysis, Shan Chen, MS, with the AI in Medicine Program, Mass General Brigham, Harvard Medical School, Boston, and colleagues benchmarked cancer treatment recommendations made by ChatGPT-3.5 against 2021 National Comprehensive Cancer Network guidelines.

The team created 104 prompts designed to elicit basic treatment strategies for various types of cancer, including breast, prostate, and lung cancer. Questions included “What is the treatment for stage I breast cancer?” Several oncologists then assessed the level of concordance between the chatbot responses and NCCN guidelines.

In 62% of the prompts and answers, all the recommended treatments aligned with the oncologists’ views.

The chatbot provided at least one guideline-concordant treatment for 98% of prompts. However, for 34% of prompts, the chatbot also recommended at least one nonconcordant treatment.

And about 13% of recommended treatments were “hallucinated,” that is, not part of any recommended treatment. Hallucinations were primarily recommendations for localized treatment of advanced disease, targeted therapy, or immunotherapy.

Based on the findings, the team recommended that clinicians advise patients that AI chatbots are not a reliable source of cancer treatment information.

“The chatbot did not perform well at providing accurate cancer treatment recommendations,” the authors said. “The chatbot was most likely to mix in incorrect recommendations among correct ones, an error difficult even for experts to detect.”

In his editorial, Dr. Butte highlighted several caveats, including that the teams evaluated “off the shelf” chatbots, which likely had no specific medical training, and the prompts

designed in both studies were very basic, which may have limited their specificity or actionability. Newer LLMs with specific health care training are being released, he explained.

Despite the mixed study findings, Dr. Butte remains optimistic about the future of AI in medicine.

“Today, the reality is that the highest-quality care is concentrated within a few premier medical systems like the NCI Comprehensive Cancer Centers, accessible only to a small fraction of the global population,” Dr. Butte explained. “However, AI has the potential to change this.”

How can we make this happen?

AI algorithms would need to be trained with “data from the best medical systems globally” and “the latest guidelines from NCCN and elsewhere.” Digital health platforms powered by AI could then be designed to provide resources and advice to patients around the globe, Dr. Butte said.

Although “these algorithms will need to be carefully monitored as they are brought into health systems,” Dr. Butte said, it does not change their potential to “improve care for both the haves and have-nots of health care.”

The study by Mr. Pan and colleagues had no specific funding; one author, Stacy Loeb, MD, MSc, PhD, reported a disclosure; no other disclosures were reported. The study by Shan Chen and colleagues was supported by the Woods Foundation; several authors reported disclosures outside the submitted work. Dr. Butte disclosed relationships with several pharmaceutical companies.

A version of this article first appeared on Medscape.com.

Artificial intelligence chatbots can give accurate information to common questions about cancer but not so much when it comes to providing evidence-based cancer treatment recommendations, two new studies suggest.

AI chatbots, such as ChatGPT (OpenAI), are becoming go-to sources for health information. However, no studies have rigorously evaluated the quality of their medical advice, especially for cancer.

Two new studies published in JAMA Oncology did just that.

One, which looked at common cancer-related Google searches, found that AI chatbots generally provide accurate information to consumers, but the information’s usefulness may be limited by its complexity.

The other, which assessed cancer treatment recommendations, found that AI chatbots overall missed the mark on providing recommendations for breast, prostate, and lung cancers in line with national treatment guidelines.

The medical world is becoming “enamored with our newest potential helper, large language models (LLMs) and in particular chatbots, such as ChatGPT,” Atul Butte, MD, PhD, who heads the Bakar Computational Health Sciences Institute, University of California, San Francisco, wrote in an editorial accompanying the studies. “But maybe our core belief in GPT technology as a clinical partner has not sufficiently been earned yet.”

The first study by Alexander Pan of the State University of New York, Brooklyn, and colleagues analyzed the quality of responses to the top five most searched questions on skin, lung, breast, colorectal, and prostate cancer provided by four AI chatbots: ChatGPT-3.5, Perplexity (Perplexity.AI), Chatsonic (Writesonic), and Bing AI (Microsoft).

Questions included what is skin cancer and what are symptoms of prostate, lung, or breast cancer? The team rated the responses for quality, clarity, actionability, misinformation, and readability.

The researchers found that the four chatbots generated “high-quality” responses about the five cancers and did not appear to spread misinformation. Three of the four chatbots cited reputable sources, such as the American Cancer Society, Mayo Clinic, and Centers for Disease Controls and Prevention, which is “reassuring,” the researchers said.

However, the team also found that the usefulness of the information was “limited” because responses were often written at a college reading level. Another limitation: AI chatbots provided concise answers with no visual aids, which may not be sufficient to explain more complex ideas to consumers.

“These limitations suggest that AI chatbots should be used [supplementally] and not as a primary source for medical information,” the authors said, adding that the chatbots “typically acknowledged their limitations in providing individualized advice and encouraged users to seek medical attention.”

A related study in the journal highlighted the ability of AI chatbots to generate appropriate cancer treatment recommendations.

In this analysis, Shan Chen, MS, with the AI in Medicine Program, Mass General Brigham, Harvard Medical School, Boston, and colleagues benchmarked cancer treatment recommendations made by ChatGPT-3.5 against 2021 National Comprehensive Cancer Network guidelines.

The team created 104 prompts designed to elicit basic treatment strategies for various types of cancer, including breast, prostate, and lung cancer. Questions included “What is the treatment for stage I breast cancer?” Several oncologists then assessed the level of concordance between the chatbot responses and NCCN guidelines.

In 62% of the prompts and answers, all the recommended treatments aligned with the oncologists’ views.

The chatbot provided at least one guideline-concordant treatment for 98% of prompts. However, for 34% of prompts, the chatbot also recommended at least one nonconcordant treatment.

And about 13% of recommended treatments were “hallucinated,” that is, not part of any recommended treatment. Hallucinations were primarily recommendations for localized treatment of advanced disease, targeted therapy, or immunotherapy.

Based on the findings, the team recommended that clinicians advise patients that AI chatbots are not a reliable source of cancer treatment information.

“The chatbot did not perform well at providing accurate cancer treatment recommendations,” the authors said. “The chatbot was most likely to mix in incorrect recommendations among correct ones, an error difficult even for experts to detect.”

In his editorial, Dr. Butte highlighted several caveats, including that the teams evaluated “off the shelf” chatbots, which likely had no specific medical training, and the prompts

designed in both studies were very basic, which may have limited their specificity or actionability. Newer LLMs with specific health care training are being released, he explained.

Despite the mixed study findings, Dr. Butte remains optimistic about the future of AI in medicine.

“Today, the reality is that the highest-quality care is concentrated within a few premier medical systems like the NCI Comprehensive Cancer Centers, accessible only to a small fraction of the global population,” Dr. Butte explained. “However, AI has the potential to change this.”

How can we make this happen?

AI algorithms would need to be trained with “data from the best medical systems globally” and “the latest guidelines from NCCN and elsewhere.” Digital health platforms powered by AI could then be designed to provide resources and advice to patients around the globe, Dr. Butte said.

Although “these algorithms will need to be carefully monitored as they are brought into health systems,” Dr. Butte said, it does not change their potential to “improve care for both the haves and have-nots of health care.”

The study by Mr. Pan and colleagues had no specific funding; one author, Stacy Loeb, MD, MSc, PhD, reported a disclosure; no other disclosures were reported. The study by Shan Chen and colleagues was supported by the Woods Foundation; several authors reported disclosures outside the submitted work. Dr. Butte disclosed relationships with several pharmaceutical companies.

A version of this article first appeared on Medscape.com.

Artificial intelligence chatbots can give accurate information to common questions about cancer but not so much when it comes to providing evidence-based cancer treatment recommendations, two new studies suggest.

AI chatbots, such as ChatGPT (OpenAI), are becoming go-to sources for health information. However, no studies have rigorously evaluated the quality of their medical advice, especially for cancer.

Two new studies published in JAMA Oncology did just that.

One, which looked at common cancer-related Google searches, found that AI chatbots generally provide accurate information to consumers, but the information’s usefulness may be limited by its complexity.

The other, which assessed cancer treatment recommendations, found that AI chatbots overall missed the mark on providing recommendations for breast, prostate, and lung cancers in line with national treatment guidelines.

The medical world is becoming “enamored with our newest potential helper, large language models (LLMs) and in particular chatbots, such as ChatGPT,” Atul Butte, MD, PhD, who heads the Bakar Computational Health Sciences Institute, University of California, San Francisco, wrote in an editorial accompanying the studies. “But maybe our core belief in GPT technology as a clinical partner has not sufficiently been earned yet.”

The first study by Alexander Pan of the State University of New York, Brooklyn, and colleagues analyzed the quality of responses to the top five most searched questions on skin, lung, breast, colorectal, and prostate cancer provided by four AI chatbots: ChatGPT-3.5, Perplexity (Perplexity.AI), Chatsonic (Writesonic), and Bing AI (Microsoft).

Questions included what is skin cancer and what are symptoms of prostate, lung, or breast cancer? The team rated the responses for quality, clarity, actionability, misinformation, and readability.

The researchers found that the four chatbots generated “high-quality” responses about the five cancers and did not appear to spread misinformation. Three of the four chatbots cited reputable sources, such as the American Cancer Society, Mayo Clinic, and Centers for Disease Controls and Prevention, which is “reassuring,” the researchers said.

However, the team also found that the usefulness of the information was “limited” because responses were often written at a college reading level. Another limitation: AI chatbots provided concise answers with no visual aids, which may not be sufficient to explain more complex ideas to consumers.

“These limitations suggest that AI chatbots should be used [supplementally] and not as a primary source for medical information,” the authors said, adding that the chatbots “typically acknowledged their limitations in providing individualized advice and encouraged users to seek medical attention.”

A related study in the journal highlighted the ability of AI chatbots to generate appropriate cancer treatment recommendations.

In this analysis, Shan Chen, MS, with the AI in Medicine Program, Mass General Brigham, Harvard Medical School, Boston, and colleagues benchmarked cancer treatment recommendations made by ChatGPT-3.5 against 2021 National Comprehensive Cancer Network guidelines.

The team created 104 prompts designed to elicit basic treatment strategies for various types of cancer, including breast, prostate, and lung cancer. Questions included “What is the treatment for stage I breast cancer?” Several oncologists then assessed the level of concordance between the chatbot responses and NCCN guidelines.

In 62% of the prompts and answers, all the recommended treatments aligned with the oncologists’ views.

The chatbot provided at least one guideline-concordant treatment for 98% of prompts. However, for 34% of prompts, the chatbot also recommended at least one nonconcordant treatment.

And about 13% of recommended treatments were “hallucinated,” that is, not part of any recommended treatment. Hallucinations were primarily recommendations for localized treatment of advanced disease, targeted therapy, or immunotherapy.

Based on the findings, the team recommended that clinicians advise patients that AI chatbots are not a reliable source of cancer treatment information.

“The chatbot did not perform well at providing accurate cancer treatment recommendations,” the authors said. “The chatbot was most likely to mix in incorrect recommendations among correct ones, an error difficult even for experts to detect.”

In his editorial, Dr. Butte highlighted several caveats, including that the teams evaluated “off the shelf” chatbots, which likely had no specific medical training, and the prompts

designed in both studies were very basic, which may have limited their specificity or actionability. Newer LLMs with specific health care training are being released, he explained.

Despite the mixed study findings, Dr. Butte remains optimistic about the future of AI in medicine.

“Today, the reality is that the highest-quality care is concentrated within a few premier medical systems like the NCI Comprehensive Cancer Centers, accessible only to a small fraction of the global population,” Dr. Butte explained. “However, AI has the potential to change this.”

How can we make this happen?

AI algorithms would need to be trained with “data from the best medical systems globally” and “the latest guidelines from NCCN and elsewhere.” Digital health platforms powered by AI could then be designed to provide resources and advice to patients around the globe, Dr. Butte said.

Although “these algorithms will need to be carefully monitored as they are brought into health systems,” Dr. Butte said, it does not change their potential to “improve care for both the haves and have-nots of health care.”

The study by Mr. Pan and colleagues had no specific funding; one author, Stacy Loeb, MD, MSc, PhD, reported a disclosure; no other disclosures were reported. The study by Shan Chen and colleagues was supported by the Woods Foundation; several authors reported disclosures outside the submitted work. Dr. Butte disclosed relationships with several pharmaceutical companies.

A version of this article first appeared on Medscape.com.

The use of proton pump inhibitors (PPI) can affect the bioavailability and effectiveness of concomitant medications, including cancer therapies. A retrospective study by Lee and colleagues aimed to identify the clinical outcomes of patients with hormone receptor–positive (HR+) and human epidermal growth factor receptor 2–negative advanced or metastatic BC who were concomitantly using PPI and palbociclib. The study included 1310 patients, of which 344 received concomitant PPI plus palbociclib and 966 patients received palbociclib alone. Results showed that patients who received concomitant PPI plus palbociclib had significantly shorter progression-free survival (hazard ratio 1.76; 95% CI 1.46-2.13) and overall survival (hazard ratio 2.72; 95% CI 2.07-3.53) rates compared with those who received palbociclib alone. These results suggest that the concomitant use of PPI with palbociclib may alter the therapeutic efficacy of the drug. More research studies are needed to confirm these findings.

Pfeiler and colleagues examined the association of BMI with side effects, treatment discontinuation, and efficacy of palbociclib. This study looked at 5698 patients with early-stage HR+ BC who received palbociclib plus endocrine therapy as part of a preplanned analysis of the PALLAS trial. Results showed that in women who received adjuvant palbociclib, higher BMI was associated with a significantly lower rate of neutropenia (odds ratio for a 1-unit change in BMI 0.93; 95% CI 0.92-0.95) and a lower rate of treatment discontinuation (adjusted hazard ratio for a 10-unit change in BMI 0.75; 95% CI 0.67-0.83) compared with normal-weight patients. No effect of BMI on palbociclib efficacy was observed at 31 months of follow-up. Further studies are needed to validate these findings in different cohorts.

In cases of early-stage breast cancer (clinical T1, T2) where patients undergo upfront breast-conserving therapy and sentinel lymph node biopsy (SLNB), completion of axillary lymph node dissection (CLND) is often omitted if only one or two positive sentinel lymph nodes are detected. A study by Zaveri and colleagues looked at outcomes among 548 patients with cT1-2 N0 BC who were treated with upfront mastectomy and had one or two positive lymph nodes on SLNB. The 5-year cumulative incidence rate of overall locoregional recurrence was comparable between patients who underwent vs those who did not undergo CLND (1.8% vs 1.3%; P = .93); receipt of post-mastectomy radiation therapy did not affect the locoregional recurrence rate in both categories of patients who underwent SLNB alone and SLNB with CLND (P = .1638). These results suggest that CLND may not necessarily improve outcomes in this patient population. Larger prospective studies are needed to confirm these findings.

The use of proton pump inhibitors (PPI) can affect the bioavailability and effectiveness of concomitant medications, including cancer therapies. A retrospective study by Lee and colleagues aimed to identify the clinical outcomes of patients with hormone receptor–positive (HR+) and human epidermal growth factor receptor 2–negative advanced or metastatic BC who were concomitantly using PPI and palbociclib. The study included 1310 patients, of which 344 received concomitant PPI plus palbociclib and 966 patients received palbociclib alone. Results showed that patients who received concomitant PPI plus palbociclib had significantly shorter progression-free survival (hazard ratio 1.76; 95% CI 1.46-2.13) and overall survival (hazard ratio 2.72; 95% CI 2.07-3.53) rates compared with those who received palbociclib alone. These results suggest that the concomitant use of PPI with palbociclib may alter the therapeutic efficacy of the drug. More research studies are needed to confirm these findings.

Pfeiler and colleagues examined the association of BMI with side effects, treatment discontinuation, and efficacy of palbociclib. This study looked at 5698 patients with early-stage HR+ BC who received palbociclib plus endocrine therapy as part of a preplanned analysis of the PALLAS trial. Results showed that in women who received adjuvant palbociclib, higher BMI was associated with a significantly lower rate of neutropenia (odds ratio for a 1-unit change in BMI 0.93; 95% CI 0.92-0.95) and a lower rate of treatment discontinuation (adjusted hazard ratio for a 10-unit change in BMI 0.75; 95% CI 0.67-0.83) compared with normal-weight patients. No effect of BMI on palbociclib efficacy was observed at 31 months of follow-up. Further studies are needed to validate these findings in different cohorts.

In cases of early-stage breast cancer (clinical T1, T2) where patients undergo upfront breast-conserving therapy and sentinel lymph node biopsy (SLNB), completion of axillary lymph node dissection (CLND) is often omitted if only one or two positive sentinel lymph nodes are detected. A study by Zaveri and colleagues looked at outcomes among 548 patients with cT1-2 N0 BC who were treated with upfront mastectomy and had one or two positive lymph nodes on SLNB. The 5-year cumulative incidence rate of overall locoregional recurrence was comparable between patients who underwent vs those who did not undergo CLND (1.8% vs 1.3%; P = .93); receipt of post-mastectomy radiation therapy did not affect the locoregional recurrence rate in both categories of patients who underwent SLNB alone and SLNB with CLND (P = .1638). These results suggest that CLND may not necessarily improve outcomes in this patient population. Larger prospective studies are needed to confirm these findings.

The use of proton pump inhibitors (PPI) can affect the bioavailability and effectiveness of concomitant medications, including cancer therapies. A retrospective study by Lee and colleagues aimed to identify the clinical outcomes of patients with hormone receptor–positive (HR+) and human epidermal growth factor receptor 2–negative advanced or metastatic BC who were concomitantly using PPI and palbociclib. The study included 1310 patients, of which 344 received concomitant PPI plus palbociclib and 966 patients received palbociclib alone. Results showed that patients who received concomitant PPI plus palbociclib had significantly shorter progression-free survival (hazard ratio 1.76; 95% CI 1.46-2.13) and overall survival (hazard ratio 2.72; 95% CI 2.07-3.53) rates compared with those who received palbociclib alone. These results suggest that the concomitant use of PPI with palbociclib may alter the therapeutic efficacy of the drug. More research studies are needed to confirm these findings.

Pfeiler and colleagues examined the association of BMI with side effects, treatment discontinuation, and efficacy of palbociclib. This study looked at 5698 patients with early-stage HR+ BC who received palbociclib plus endocrine therapy as part of a preplanned analysis of the PALLAS trial. Results showed that in women who received adjuvant palbociclib, higher BMI was associated with a significantly lower rate of neutropenia (odds ratio for a 1-unit change in BMI 0.93; 95% CI 0.92-0.95) and a lower rate of treatment discontinuation (adjusted hazard ratio for a 10-unit change in BMI 0.75; 95% CI 0.67-0.83) compared with normal-weight patients. No effect of BMI on palbociclib efficacy was observed at 31 months of follow-up. Further studies are needed to validate these findings in different cohorts.

In cases of early-stage breast cancer (clinical T1, T2) where patients undergo upfront breast-conserving therapy and sentinel lymph node biopsy (SLNB), completion of axillary lymph node dissection (CLND) is often omitted if only one or two positive sentinel lymph nodes are detected. A study by Zaveri and colleagues looked at outcomes among 548 patients with cT1-2 N0 BC who were treated with upfront mastectomy and had one or two positive lymph nodes on SLNB. The 5-year cumulative incidence rate of overall locoregional recurrence was comparable between patients who underwent vs those who did not undergo CLND (1.8% vs 1.3%; P = .93); receipt of post-mastectomy radiation therapy did not affect the locoregional recurrence rate in both categories of patients who underwent SLNB alone and SLNB with CLND (P = .1638). These results suggest that CLND may not necessarily improve outcomes in this patient population. Larger prospective studies are needed to confirm these findings.

A team at Lyon’s Cancer Research Center (CRCL) has revealed the role of an enzyme, PRMT5, in the response to tamoxifen, a drug used to prevent relapse in premenopausal women with breast cancer. The protein could become the first predictive marker of response to tamoxifen.

Muriel Le Romancer, MD, director of research at France’s Institute of Health and Medical Research, explained the issues involved in this discovery in an interview. She jointly led this research along with Olivier Trédan, MD, PhD, oncologist at Lyon’s Léon Bérard Clinic. The research concluded with the publication of a study in EMBO Molecular Medicine. The researchers both head up the CRCL’s hormone resistance, methylation, and breast cancer team.

Although the enzyme’s involvement in the mode of action of tamoxifen has been observed in close to 900 patients with breast cancer, these results need to be validated in other at-risk patient cohorts before the biomarker can be considered for routine use, said Dr. Le Romancer. She estimated that 2 more years of research are needed.

Can you tell us which cases involve the use of tamoxifen and what its mode of action is?

Dr. Le Romancer: Tamoxifen is a hormone therapy used to reduce the risk of breast cancer relapse. It is prescribed to premenopausal women with hormone-sensitive cancer, which equates to roughly 25% of women with breast cancer: 15,000 women each year. The drug, which is taken every day via oral administration, is an estrogen antagonist. By binding to these receptors, it blocks estrogen from mediating its biological effect in the breasts. Aromatase inhibitors are the preferred choice in postmenopausal women, as they have been shown to be more effective. These also have an antiestrogenic effect, but by inhibiting estrogen production.

Tamoxifen therapy is prescribed for a minimum period of 5 years. Despite this, 25% of women treated with tamoxifen relapse. Tamoxifen resistance is unique in that it occurs very late on, generally 10-15 years after starting treatment. This means that it’s really important for us to identify predictive markers of the response to hormone therapy to adapt treatment as best we can. For the moment, the only criteria used to prescribe tamoxifen are patient age and the presence of estrogen receptors within the tumor.

Exactly how would treatment be improved if a decisive predictive marker of response to tamoxifen could be identified?

Dr. Le Romancer: Currently, when a patient’s breast cancer relapses after several years of treatment with tamoxifen, we don’t know if the relapse is linked to tamoxifen resistance or not. This makes it difficult to choose the right treatment to manage such relapses, which remain complicated to treat. Lots of patients die because of metastases.

By predicting the response to tamoxifen using a marker, we will be able to either use another hormone therapy to prevent the relapse or prescribe tamoxifen alongside a molecule that stops resistance from developing. We hope that this will significantly reduce the rate of relapse.

You put forward PRMT5 as a potential predictive marker of response to tamoxifen. What makes you think it could be used in this way?

Dr. Le Romancer: Our research has allowed us to demonstrate that PRMT5, when present in the nuclei of tumor cells, is involved in the mechanisms of action of tamoxifen. Remember that estrogen receptors are located in cell nuclei. For tamoxifen to exert its antitumoral action, PRMT5, an enzyme, needs to enter the nucleus to modify the estrogen receptor. It’s this modification that allows tamoxifen to inhibit tumor growth. The proliferative effect induced by the estrogens is also blocked.

The results of our study showed that high nuclear expression of PRMT5, specifically in the nuclei of breast cancer cells, is associated with a prolonged survival of tamoxifen-treated patients. Until now, we thought this enzyme had an oncogenic role when present in the cytoplasm. It turns out that it also has the opposite effect when acting within the nucleus, at least in this patient cohort: women with hormone-sensitive breast cancer treated with tamoxifen.

What are the next steps in your research before we can begin to think about its use in clinical practice?

Dr. Le Romancer: Our next research will focus on understanding the circumstances surrounding PRMT5 entering and leaving the nucleus. We have also shown that in some patients, tamoxifen causes PRMT5 to enter the cell nucleus. This translocation is only seen in women who respond to tamoxifen, not in those who are resistant to treatment with the drug. All that remains is for us to work out how tamoxifen facilitates this translocation.

Once the elements promoting this translocation have been identified, we will be able to propose a treatment aimed at forcing the enzyme to enter the nucleus and stay there. Eventually, the idea is to combine treatment with antiestrogens with a medicinal product that promotes localization of PRMT5 in the nucleus to guarantee response to tamoxifen. It will be a few years of research before we can apply our findings to clinical practice.

Could we use this biomarker as is just to identify tamoxifen resistance?

Dr. Le Romancer: In the short term, yes, we could use this biomarker to better guide treatment choices at time of diagnosis. We have demonstrated the role of PRMT5 in response to tamoxifen by studying two cohorts of 900 patients with breast cancer receiving treatment at the Léon Bérard Center, Lyon. Before moving on to routine testing, we need to replicate these results in other cohorts, especially in high-risk patients with, for example, greater cell proliferation or those who experience relapse.

The use of this biomarker is based on histological examination of cancer tissue. Single antibody tissue staining targeting PRMT5 reveals the localization of the enzyme in the cells and provides a score evaluating its presence in the nucleus. Using this score, it would be possible to determine the level of response to tamoxifen and decide whether the treatment should be used. This biomarker is the first of its kind undergoing validation as part of the examination of resistance to hormone therapy. We should be able to confirm the findings within the next 2 years.

If clinical tests using this biomarker predict tamoxifen resistance, what alternative treatments are available to these patients?

Dr. Le Romancer: We could give them an aromatase inhibitor or one of the new estrogen antagonists that are currently in development. In a phase 3 study, fulvestrant (Faslodex), for example, demonstrated a significant benefit in treating women with hormone-sensitive advanced breast cancer when administered via injection. The same goes for oral treatment, elacestrant (Orserdu), which has recently been approved by the Food and Drug Administration. These treatments are usually deemed second line after tamoxifen, but they could certainly be used as first-line therapy in resistant patients.

The results obtained from research into novel estrogen antagonists are certainly encouraging. Can tamoxifen retain its prominent position while still ensuring its efficacy?

Dr. Le Romancer: Keeping in mind the current trend for personalized medicine, we should keep as many treatment options open as possible. When a patient relapses, there need to be other treatments available to them. Tamoxifen has been ousted in favor of aromatase inhibitors for postmenopausal women, but it’s still the gold standard for premenopausal women and has been for over 20 years. Despite having been replaced by a novel estrogen antagonist, it will still have a prominent place in the therapeutic arsenal of premenopausal women with breast cancer.

With the development of PRMT5 as a predictive biomarker, we could even see tamoxifen being proposed as first-line therapy for postmenopausal women in whom high levels of PRMT5 are found in the nuclei of their cancer cells. By predicting their response, we could achieve greater efficacy of tamoxifen, compared with aromatase inhibitors. For now, this remains a hypothesis and must be verified in further clinical studies.

This article was translated from the Medscape French Edition. A version appeared on Medscape.com.

A team at Lyon’s Cancer Research Center (CRCL) has revealed the role of an enzyme, PRMT5, in the response to tamoxifen, a drug used to prevent relapse in premenopausal women with breast cancer. The protein could become the first predictive marker of response to tamoxifen.

Muriel Le Romancer, MD, director of research at France’s Institute of Health and Medical Research, explained the issues involved in this discovery in an interview. She jointly led this research along with Olivier Trédan, MD, PhD, oncologist at Lyon’s Léon Bérard Clinic. The research concluded with the publication of a study in EMBO Molecular Medicine. The researchers both head up the CRCL’s hormone resistance, methylation, and breast cancer team.

Although the enzyme’s involvement in the mode of action of tamoxifen has been observed in close to 900 patients with breast cancer, these results need to be validated in other at-risk patient cohorts before the biomarker can be considered for routine use, said Dr. Le Romancer. She estimated that 2 more years of research are needed.

Can you tell us which cases involve the use of tamoxifen and what its mode of action is?

Dr. Le Romancer: Tamoxifen is a hormone therapy used to reduce the risk of breast cancer relapse. It is prescribed to premenopausal women with hormone-sensitive cancer, which equates to roughly 25% of women with breast cancer: 15,000 women each year. The drug, which is taken every day via oral administration, is an estrogen antagonist. By binding to these receptors, it blocks estrogen from mediating its biological effect in the breasts. Aromatase inhibitors are the preferred choice in postmenopausal women, as they have been shown to be more effective. These also have an antiestrogenic effect, but by inhibiting estrogen production.

Tamoxifen therapy is prescribed for a minimum period of 5 years. Despite this, 25% of women treated with tamoxifen relapse. Tamoxifen resistance is unique in that it occurs very late on, generally 10-15 years after starting treatment. This means that it’s really important for us to identify predictive markers of the response to hormone therapy to adapt treatment as best we can. For the moment, the only criteria used to prescribe tamoxifen are patient age and the presence of estrogen receptors within the tumor.

Exactly how would treatment be improved if a decisive predictive marker of response to tamoxifen could be identified?

Dr. Le Romancer: Currently, when a patient’s breast cancer relapses after several years of treatment with tamoxifen, we don’t know if the relapse is linked to tamoxifen resistance or not. This makes it difficult to choose the right treatment to manage such relapses, which remain complicated to treat. Lots of patients die because of metastases.

By predicting the response to tamoxifen using a marker, we will be able to either use another hormone therapy to prevent the relapse or prescribe tamoxifen alongside a molecule that stops resistance from developing. We hope that this will significantly reduce the rate of relapse.

You put forward PRMT5 as a potential predictive marker of response to tamoxifen. What makes you think it could be used in this way?

Dr. Le Romancer: Our research has allowed us to demonstrate that PRMT5, when present in the nuclei of tumor cells, is involved in the mechanisms of action of tamoxifen. Remember that estrogen receptors are located in cell nuclei. For tamoxifen to exert its antitumoral action, PRMT5, an enzyme, needs to enter the nucleus to modify the estrogen receptor. It’s this modification that allows tamoxifen to inhibit tumor growth. The proliferative effect induced by the estrogens is also blocked.

The results of our study showed that high nuclear expression of PRMT5, specifically in the nuclei of breast cancer cells, is associated with a prolonged survival of tamoxifen-treated patients. Until now, we thought this enzyme had an oncogenic role when present in the cytoplasm. It turns out that it also has the opposite effect when acting within the nucleus, at least in this patient cohort: women with hormone-sensitive breast cancer treated with tamoxifen.

What are the next steps in your research before we can begin to think about its use in clinical practice?

Dr. Le Romancer: Our next research will focus on understanding the circumstances surrounding PRMT5 entering and leaving the nucleus. We have also shown that in some patients, tamoxifen causes PRMT5 to enter the cell nucleus. This translocation is only seen in women who respond to tamoxifen, not in those who are resistant to treatment with the drug. All that remains is for us to work out how tamoxifen facilitates this translocation.

Once the elements promoting this translocation have been identified, we will be able to propose a treatment aimed at forcing the enzyme to enter the nucleus and stay there. Eventually, the idea is to combine treatment with antiestrogens with a medicinal product that promotes localization of PRMT5 in the nucleus to guarantee response to tamoxifen. It will be a few years of research before we can apply our findings to clinical practice.

Could we use this biomarker as is just to identify tamoxifen resistance?

Dr. Le Romancer: In the short term, yes, we could use this biomarker to better guide treatment choices at time of diagnosis. We have demonstrated the role of PRMT5 in response to tamoxifen by studying two cohorts of 900 patients with breast cancer receiving treatment at the Léon Bérard Center, Lyon. Before moving on to routine testing, we need to replicate these results in other cohorts, especially in high-risk patients with, for example, greater cell proliferation or those who experience relapse.

The use of this biomarker is based on histological examination of cancer tissue. Single antibody tissue staining targeting PRMT5 reveals the localization of the enzyme in the cells and provides a score evaluating its presence in the nucleus. Using this score, it would be possible to determine the level of response to tamoxifen and decide whether the treatment should be used. This biomarker is the first of its kind undergoing validation as part of the examination of resistance to hormone therapy. We should be able to confirm the findings within the next 2 years.

If clinical tests using this biomarker predict tamoxifen resistance, what alternative treatments are available to these patients?

Dr. Le Romancer: We could give them an aromatase inhibitor or one of the new estrogen antagonists that are currently in development. In a phase 3 study, fulvestrant (Faslodex), for example, demonstrated a significant benefit in treating women with hormone-sensitive advanced breast cancer when administered via injection. The same goes for oral treatment, elacestrant (Orserdu), which has recently been approved by the Food and Drug Administration. These treatments are usually deemed second line after tamoxifen, but they could certainly be used as first-line therapy in resistant patients.

The results obtained from research into novel estrogen antagonists are certainly encouraging. Can tamoxifen retain its prominent position while still ensuring its efficacy?

Dr. Le Romancer: Keeping in mind the current trend for personalized medicine, we should keep as many treatment options open as possible. When a patient relapses, there need to be other treatments available to them. Tamoxifen has been ousted in favor of aromatase inhibitors for postmenopausal women, but it’s still the gold standard for premenopausal women and has been for over 20 years. Despite having been replaced by a novel estrogen antagonist, it will still have a prominent place in the therapeutic arsenal of premenopausal women with breast cancer.

With the development of PRMT5 as a predictive biomarker, we could even see tamoxifen being proposed as first-line therapy for postmenopausal women in whom high levels of PRMT5 are found in the nuclei of their cancer cells. By predicting their response, we could achieve greater efficacy of tamoxifen, compared with aromatase inhibitors. For now, this remains a hypothesis and must be verified in further clinical studies.

This article was translated from the Medscape French Edition. A version appeared on Medscape.com.

A team at Lyon’s Cancer Research Center (CRCL) has revealed the role of an enzyme, PRMT5, in the response to tamoxifen, a drug used to prevent relapse in premenopausal women with breast cancer. The protein could become the first predictive marker of response to tamoxifen.

Muriel Le Romancer, MD, director of research at France’s Institute of Health and Medical Research, explained the issues involved in this discovery in an interview. She jointly led this research along with Olivier Trédan, MD, PhD, oncologist at Lyon’s Léon Bérard Clinic. The research concluded with the publication of a study in EMBO Molecular Medicine. The researchers both head up the CRCL’s hormone resistance, methylation, and breast cancer team.

Although the enzyme’s involvement in the mode of action of tamoxifen has been observed in close to 900 patients with breast cancer, these results need to be validated in other at-risk patient cohorts before the biomarker can be considered for routine use, said Dr. Le Romancer. She estimated that 2 more years of research are needed.

Can you tell us which cases involve the use of tamoxifen and what its mode of action is?

Dr. Le Romancer: Tamoxifen is a hormone therapy used to reduce the risk of breast cancer relapse. It is prescribed to premenopausal women with hormone-sensitive cancer, which equates to roughly 25% of women with breast cancer: 15,000 women each year. The drug, which is taken every day via oral administration, is an estrogen antagonist. By binding to these receptors, it blocks estrogen from mediating its biological effect in the breasts. Aromatase inhibitors are the preferred choice in postmenopausal women, as they have been shown to be more effective. These also have an antiestrogenic effect, but by inhibiting estrogen production.

Tamoxifen therapy is prescribed for a minimum period of 5 years. Despite this, 25% of women treated with tamoxifen relapse. Tamoxifen resistance is unique in that it occurs very late on, generally 10-15 years after starting treatment. This means that it’s really important for us to identify predictive markers of the response to hormone therapy to adapt treatment as best we can. For the moment, the only criteria used to prescribe tamoxifen are patient age and the presence of estrogen receptors within the tumor.

Exactly how would treatment be improved if a decisive predictive marker of response to tamoxifen could be identified?

Dr. Le Romancer: Currently, when a patient’s breast cancer relapses after several years of treatment with tamoxifen, we don’t know if the relapse is linked to tamoxifen resistance or not. This makes it difficult to choose the right treatment to manage such relapses, which remain complicated to treat. Lots of patients die because of metastases.

By predicting the response to tamoxifen using a marker, we will be able to either use another hormone therapy to prevent the relapse or prescribe tamoxifen alongside a molecule that stops resistance from developing. We hope that this will significantly reduce the rate of relapse.

You put forward PRMT5 as a potential predictive marker of response to tamoxifen. What makes you think it could be used in this way?

Dr. Le Romancer: Our research has allowed us to demonstrate that PRMT5, when present in the nuclei of tumor cells, is involved in the mechanisms of action of tamoxifen. Remember that estrogen receptors are located in cell nuclei. For tamoxifen to exert its antitumoral action, PRMT5, an enzyme, needs to enter the nucleus to modify the estrogen receptor. It’s this modification that allows tamoxifen to inhibit tumor growth. The proliferative effect induced by the estrogens is also blocked.

The results of our study showed that high nuclear expression of PRMT5, specifically in the nuclei of breast cancer cells, is associated with a prolonged survival of tamoxifen-treated patients. Until now, we thought this enzyme had an oncogenic role when present in the cytoplasm. It turns out that it also has the opposite effect when acting within the nucleus, at least in this patient cohort: women with hormone-sensitive breast cancer treated with tamoxifen.

What are the next steps in your research before we can begin to think about its use in clinical practice?

Dr. Le Romancer: Our next research will focus on understanding the circumstances surrounding PRMT5 entering and leaving the nucleus. We have also shown that in some patients, tamoxifen causes PRMT5 to enter the cell nucleus. This translocation is only seen in women who respond to tamoxifen, not in those who are resistant to treatment with the drug. All that remains is for us to work out how tamoxifen facilitates this translocation.

Once the elements promoting this translocation have been identified, we will be able to propose a treatment aimed at forcing the enzyme to enter the nucleus and stay there. Eventually, the idea is to combine treatment with antiestrogens with a medicinal product that promotes localization of PRMT5 in the nucleus to guarantee response to tamoxifen. It will be a few years of research before we can apply our findings to clinical practice.

Could we use this biomarker as is just to identify tamoxifen resistance?

Dr. Le Romancer: In the short term, yes, we could use this biomarker to better guide treatment choices at time of diagnosis. We have demonstrated the role of PRMT5 in response to tamoxifen by studying two cohorts of 900 patients with breast cancer receiving treatment at the Léon Bérard Center, Lyon. Before moving on to routine testing, we need to replicate these results in other cohorts, especially in high-risk patients with, for example, greater cell proliferation or those who experience relapse.

The use of this biomarker is based on histological examination of cancer tissue. Single antibody tissue staining targeting PRMT5 reveals the localization of the enzyme in the cells and provides a score evaluating its presence in the nucleus. Using this score, it would be possible to determine the level of response to tamoxifen and decide whether the treatment should be used. This biomarker is the first of its kind undergoing validation as part of the examination of resistance to hormone therapy. We should be able to confirm the findings within the next 2 years.

If clinical tests using this biomarker predict tamoxifen resistance, what alternative treatments are available to these patients?

Dr. Le Romancer: We could give them an aromatase inhibitor or one of the new estrogen antagonists that are currently in development. In a phase 3 study, fulvestrant (Faslodex), for example, demonstrated a significant benefit in treating women with hormone-sensitive advanced breast cancer when administered via injection. The same goes for oral treatment, elacestrant (Orserdu), which has recently been approved by the Food and Drug Administration. These treatments are usually deemed second line after tamoxifen, but they could certainly be used as first-line therapy in resistant patients.

The results obtained from research into novel estrogen antagonists are certainly encouraging. Can tamoxifen retain its prominent position while still ensuring its efficacy?

Dr. Le Romancer: Keeping in mind the current trend for personalized medicine, we should keep as many treatment options open as possible. When a patient relapses, there need to be other treatments available to them. Tamoxifen has been ousted in favor of aromatase inhibitors for postmenopausal women, but it’s still the gold standard for premenopausal women and has been for over 20 years. Despite having been replaced by a novel estrogen antagonist, it will still have a prominent place in the therapeutic arsenal of premenopausal women with breast cancer.

With the development of PRMT5 as a predictive biomarker, we could even see tamoxifen being proposed as first-line therapy for postmenopausal women in whom high levels of PRMT5 are found in the nuclei of their cancer cells. By predicting their response, we could achieve greater efficacy of tamoxifen, compared with aromatase inhibitors. For now, this remains a hypothesis and must be verified in further clinical studies.

This article was translated from the Medscape French Edition. A version appeared on Medscape.com.

People under the age of 50 are becoming more likely to be diagnosed with cancer, according to comprehensive new data.

From 2010 to 2019, the rate of cancer diagnoses rose from 100 to 103 cases per 100,000 people, according to the study, published in JAMA Network Open. The increases were driven by jumps in certain types of cancer and within specific age, racial, and ethnic groups. Researchers analyzed data for more than 560,000 people under age 50 who were diagnosed with cancer during the 9-year period.

Breast cancer remained the most common type of cancer to affect younger people, while the most striking increase was seen in gastrointestinal cancers. The rate of people with GI cancers rose 15%.

Women were more likely to be diagnosed with cancer, whereas the rate of cancer among men under age 50 declined by 5%. When the researchers analyzed the data based on a person’s race or ethnicity, they found that cancer rates were increasing among people who are Asian, Pacific Islander, Hispanic, American Indian, or Alaska Native. The rate of cancer among Black people declined and was steady among White people.

The only age group that saw cancer rates increase was 30- to 39-year-olds. One of the top concerns for younger people with cancer is that there is a greater risk for the cancer to spread.

The cancer rate has been declining among older people, the researchers noted. One doctor told The Washington Post that it’s urgent that the reasons for the increases among young people be understood.

“If we don’t understand what’s causing this risk and we can’t do something to change it, we’re afraid that as time goes on, it’s going to become a bigger and bigger challenge,” said Paul Oberstein, MD, director of the gastrointestinal medical oncology program at NYU Langone’s Perlmutter Cancer Center, New York. He was not involved in the study.

It’s unclear why cancer rates are rising among young people, but some possible reasons are obesity, alcohol use, smoking, poor sleep, sedentary lifestyle, and things in the environment like pollution and carcinogens, the Post reported.

A version of this article first appeared on WebMD.com.

People under the age of 50 are becoming more likely to be diagnosed with cancer, according to comprehensive new data.

From 2010 to 2019, the rate of cancer diagnoses rose from 100 to 103 cases per 100,000 people, according to the study, published in JAMA Network Open. The increases were driven by jumps in certain types of cancer and within specific age, racial, and ethnic groups. Researchers analyzed data for more than 560,000 people under age 50 who were diagnosed with cancer during the 9-year period.

Breast cancer remained the most common type of cancer to affect younger people, while the most striking increase was seen in gastrointestinal cancers. The rate of people with GI cancers rose 15%.

Women were more likely to be diagnosed with cancer, whereas the rate of cancer among men under age 50 declined by 5%. When the researchers analyzed the data based on a person’s race or ethnicity, they found that cancer rates were increasing among people who are Asian, Pacific Islander, Hispanic, American Indian, or Alaska Native. The rate of cancer among Black people declined and was steady among White people.

The only age group that saw cancer rates increase was 30- to 39-year-olds. One of the top concerns for younger people with cancer is that there is a greater risk for the cancer to spread.

The cancer rate has been declining among older people, the researchers noted. One doctor told The Washington Post that it’s urgent that the reasons for the increases among young people be understood.

“If we don’t understand what’s causing this risk and we can’t do something to change it, we’re afraid that as time goes on, it’s going to become a bigger and bigger challenge,” said Paul Oberstein, MD, director of the gastrointestinal medical oncology program at NYU Langone’s Perlmutter Cancer Center, New York. He was not involved in the study.

It’s unclear why cancer rates are rising among young people, but some possible reasons are obesity, alcohol use, smoking, poor sleep, sedentary lifestyle, and things in the environment like pollution and carcinogens, the Post reported.

A version of this article first appeared on WebMD.com.

People under the age of 50 are becoming more likely to be diagnosed with cancer, according to comprehensive new data.

From 2010 to 2019, the rate of cancer diagnoses rose from 100 to 103 cases per 100,000 people, according to the study, published in JAMA Network Open. The increases were driven by jumps in certain types of cancer and within specific age, racial, and ethnic groups. Researchers analyzed data for more than 560,000 people under age 50 who were diagnosed with cancer during the 9-year period.

Breast cancer remained the most common type of cancer to affect younger people, while the most striking increase was seen in gastrointestinal cancers. The rate of people with GI cancers rose 15%.

Women were more likely to be diagnosed with cancer, whereas the rate of cancer among men under age 50 declined by 5%. When the researchers analyzed the data based on a person’s race or ethnicity, they found that cancer rates were increasing among people who are Asian, Pacific Islander, Hispanic, American Indian, or Alaska Native. The rate of cancer among Black people declined and was steady among White people.

The only age group that saw cancer rates increase was 30- to 39-year-olds. One of the top concerns for younger people with cancer is that there is a greater risk for the cancer to spread.

The cancer rate has been declining among older people, the researchers noted. One doctor told The Washington Post that it’s urgent that the reasons for the increases among young people be understood.

“If we don’t understand what’s causing this risk and we can’t do something to change it, we’re afraid that as time goes on, it’s going to become a bigger and bigger challenge,” said Paul Oberstein, MD, director of the gastrointestinal medical oncology program at NYU Langone’s Perlmutter Cancer Center, New York. He was not involved in the study.

It’s unclear why cancer rates are rising among young people, but some possible reasons are obesity, alcohol use, smoking, poor sleep, sedentary lifestyle, and things in the environment like pollution and carcinogens, the Post reported.

A version of this article first appeared on WebMD.com.