This article was first published on October 31, 2018, and updated on October 20, 2021.
Breast cancer is a global health problem. For the year 2021, the American Cancer Society has estimated that there will be approximately 281,550 new diagnoses of invasive breast cancer in women, 49,290 new cases of ductal carcinoma in situ (DCIS) diagnosed, and 43,600 deaths due to the disease within the United States alone. For the average American woman, there is a 1 in 8 chance that she will develop breast cancer during her lifetime. Though the mortality rate dropped 1 percent per year from 2013 to 2018 due to scientific advances in diagnosis and treatment, there is still a long way to go to achieve victory in the battle against breast cancer.
In the mid 1980s, October was designated by industry giants and charity organizations around the globe as the month to increase breast cancer awareness and to raise funds for its research, prevention, diagnosis, treatment, and cure. Companies, hospitals, and various agencies also promote education and provide support to those affected by breast cancer. This year, on September 30, President Biden made it official, committing to invest billions in federal funding for research into cancer and other deadly diseases. PreScouter stands with all the advocates, researchers, medical professionals, caregivers, and cancer survivors in honoring those who have lost their lives to breast cancer by updating this 2018 article on advances in the battle against breast cancer to raise awareness of the progress that has been made since then.
To support this initiative, the editorial team at PreScouter is proud to highlight four of this year’s most amazing research advances in breast cancer diagnosis and therapy.
U.S. Food and Drug Administration expanded approval for the drug ribociclib by Novartis:
On July 18, 2018, the Food and Drug Administration (FDA) expanded the approval of ribociclib (Kisqali) in combination with an aromatase inhibitor for advanced breast cancer treatment. The drug is now approved for premenopausal and perimenopausal women based on results from MONALEESA-7 randomized clinical trials and for postmenopausal women based on MONALEESA-3 trials sponsored by Novartis. The FDA also approved ribociclib as initial endocrine-based therapy or following disease progression on endocrine therapy in combination with the estrogen receptor antagonist fulvestrant for the treatment of postmenopausal women.
The approval was good news for women with advanced hormone receptor–positive (HR+), human growth factor receptor 2–negative (HER2-) cancer, as this new drug promised to provide them with a higher quality of life. In brief, ribociclib acts as an inhibitor of the cell cycle process by blocking CDK-4 and CDK-6 activity for cell division. It slows down the disease progression, thus providing more time for cancer treatment and eradication.
Today, ribociclib is indicated for treatment of all women with advanced or metastasized HR+/HER2- breast cancer. And there is, once again, good news for women with this type of cancer: Data was recently presented from the MONALEESA-2 study showing a statistically significant and clinically meaningful overall survival benefit with ribociclib plus aromatase inhibitor for postmenopausal patients with advanced HR+/HER2– breast cancer. And according to this clinical review published online on October 12, 2021, by the journal JCO Oncology Practice, the benefits of ribociclib combinations for overall survival of women with advanced breast cancer have likewise been validated by several other clinical trials in the past few years.
New therapeutic strategy for treating triple-negative breast cancer (TNBC):
TNBC is a very aggressive form of breast cancer; it does not respond to hormonal therapies targeting estrogen receptors, progesterone receptor targeters such as tamoxifen and aromatase inhibitors, or HER2+ treatments such as Herceptin. In an August 2018 article published in Nature Communications, researchers demonstrated that IRE1 protein might improve the response to chemotherapy and reduce relapse for TNBC patients. IRE1 signaling in cancer has been a much-discussed topic, as this protein possesses both kinase and endoribonuclease (RNase) activities and plays a major role in cell survival under stress conditions.
The research article emphasizes the other side of this signaling cascade, where IRE1 RNase signaling supports the tumor progression, including angiogenesis and metastasis by production of pro-tumorigenic factors in TNBC cells. The study demonstrated in a xenograft mouse model that inhibition of IRE1-RNase activity increases paclitaxel-mediated tumor suppression and delays tumor relapse post therapy. Even with chemotherapy, a large percentage of TNBC patients currently suffer a relapse and poor prognosis; IRE1 may prove to be a good therapeutic target to help these patients, pending further studies and clinical validation.
To date, even with chemotherapy, a large percentage of TNBC patients still suffer a relapse and poor prognosis; and despite ongoing efforts at developing small-molecule activators of IRE1 that could be used as therapies for TNBC and other diseases, targeting IRE1 has proven to be more difficult than was hoped. As mentioned in an article published in Biomedicines in February 2021, understanding the initiating and regulatory mechanisms involved in activation of the IRE1 molecule has been “elusive and controversial” due to the complexities of intramolecular signaling pathways and numerous other issues discussed in the article.
Hence, as researchers continue to study how the IRE1 protein functions, for most TNBC patients, chemotherapy continues to be the main systemic therapeutic option, with surgery and radiation also being common. If PD-L1 protein is present, immunotherapy may be administered; for women with a BRCA mutation, PARP inhibitors may be considered; and for advanced TNBC in which other drug treatments have been tried, the antibody-drug conjugate sacituzumab govitecan (Trodelvy) may be an option.
Google AI can diagnose breast cancer:
Histopathology is the gold standard technique for cancer staging that categorizes the tumors on the basis of TNM classification, which is based on tumor size, affected lymph nodes, and metastasis status. In breast cancer, nodal metastasis influences the treatment decisions regarding radiation therapy and chemotherapy. Thus, while crucial, a pathologist’s job is laborious and highly dependent upon years of expertise.
In October 2018, it was announced that the healthcare division of Google AI had developed an artificial intelligence (AI) algorithm, termed LYmph Node Assistant (LYNA), to improve diagnostic accuracy for breast cancer. The research was published in Archives of Pathology and Laboratory Medicine. The AI algorithm showed an accuracy of 99 percent in differentiating cancerous from noncancerous regions. The research indicates that AI could be a valuable ally, with the promise that carefully validated deep learning technologies could improve both the accuracy and availability of pathologic diagnosis around the world.
Studies conducted to validate the performance of artificial intelligence and machine learning since then have shown that this technology can aid in not only breast cancer diagnostics but also risk prediction, as this 2019 review article in the journal PLOS ONE shows. When researchers looked at the ability of machine learning models to predict breast cancer risk, they found that their machine learning model performed well when personal health inputs were included and could serve as a cost-effective non-invasive tool in the fight against breast cancer. The results of another study published in Nature Communications in 2021 show that radiologists were able to lower their false positive rates by 37 percent and decrease the need for biopsies with the aid of AI. While still a nascent field, digital oncology is expect to become the new normal for cancer care within the next decade.
A healthy diet could help to protect against cancer:
There have been a number of studies lately reporting that good eating habits lead to lower risk of breast cancer. An article published in the journal Clinical and Experimental Metastasis proposed the potential therapeutic role of dietary long-chain omega-3 fatty acids, which are commonly found in products containing fish oil, in the control of tumor growth and metastasis. The epidemiological study indicated that dietary consumption of omega-3 fatty acids can reduce the risk of breast cancer as well as prolong survival in mice implanted with mammary tumor cells.
A review article published in Molecular Medicine elaborates on how plant-based polyphenols target multiple signaling pathways that regulate key cellular processes and may aid in inhibiting metastasis and regulating proliferation, apoptosis, and differentiation of tumor cells, thus suppressing breast cancer growth by controlling the tumor microenvironment. These compounds could thus be promising candidates for supplements to traditional cancer prevention and treatment regimes, and they could also inform efforts to design novel synthetic drugs. Another recent article, published in October 2018 in Cell Reports, indicates that diet modulates mammary gland microbiota populations in a nonhuman primate model. In this study, researchers observed that consumption of a Mediterranean diet increased the abundance of mammary gland–specific microbiome populations, which may represent a potential mechanism by which diet can modulate risk of developing breast cancer.
There have been a number of studies reporting that good eating habits lead to lower risk of breast cancer. An article published in the journal Clinical and Experimental Metastasis in October 2018 proposed the potential therapeutic role of dietary long-chain omega-3 fatty acids, which are commonly found in products containing fish oil, in the control of tumor growth and metastasis. The epidemiological study indicated that dietary consumption of omega-3 fatty acids can reduce the risk of breast cancer as well as prolong survival in mice implanted with mammary tumor cells.
A review article published in Molecular Medicine in June 2018 elaborates on how plant-based polyphenols target multiple signaling pathways that regulate key cellular processes and may aid in inhibiting metastasis and regulating proliferation, apoptosis, and differentiation of tumor cells, thus suppressing breast cancer growth by controlling the tumor microenvironment. These compounds could thus be promising candidates for supplements to traditional cancer prevention and treatment regimes, and they could also inform efforts to design novel synthetic drugs. Another article published in October 2018 in Cell Reports indicates that diet modulates mammary gland microbiota populations in a nonhuman primate model. In this study, researchers observed that consumption of a Mediterranean diet increased the abundance of mammary gland–specific microbiome populations, which may represent a potential mechanism by which diet can modulate risk of developing breast cancer.
More recent studies and reviews investigating such topics as the relationship between diet and cancer, the anti-cancer mechanisms of flavonoids, and the connection between microbiota and cancer are opening up further possibilities for addressing breast cancer through diet as well as through bacterial therapies.
Conclusion:
In summary, research in various disciplines is moving forward our knowledge of breast cancer treatment, diagnosis, and prevention. From targeted drugs to uses of AI and better understandings of the positive effects of diet, although some mechanisms have proven to be vexingly complex, researchers continue the dedicated work of discovering new and promising tools to fight the battle against breast cancer.
