{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:37:25Z","timestamp":1790620645215,"version":"4.1.0"},"reference-count":86,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-178260"],"award-info":[{"award-number":["PJT-178260"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Canadian Cancer Society Doctoral Research Training Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: n-3 PUFA derived from marine sources, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), exhibit potential for breast cancer prevention. In contrast, higher dietary intakes of n-6 PUFA, such as linoleic acid (LA), have been implicated in promoting mammary tumourigenesis. However, there is a need for further exploration into how n-3 PUFA influence breast cancer development in comparison to different amounts and sources of LA. Objective: The purpose of this study was to compare the effects of n-3 PUFA-enriched diets versus n-6 PUFA diets differing in LA content, including corn oil (50% LA) and safflower oil (70% LA), on mammary tumour development in a HER2+ breast cancer model. Methods: Using the HER2+ breast cancer MMTV-neu(ndl)YD5 transgenic mouse model, this study determined the effects of: (1) 10% w\/w corn oil (CO, n-6 PUFA, n = 14), (2) 10% w\/w safflower oil (SO, n-6 PUFA, n = 14), (3) 3% w\/w menhaden oil + 7% w\/w CO (3% FO 7% CO, n-3 PUFA, n = 12), and (4) 3% w\/w menhaden oil + 7% w\/w SO (3% FO 7% SO, n-3 PUFA, n = 14) on puberty onset, tumour incidence, tumour volume, and tumour number in utero until 20 weeks of age. Results: Mice fed the n-3 PUFA-enriched diets showed a lower trajectory of tumour development compared to the n-6 PUFA diets, although the differences for palpated tumour volume and number over time reached significance only between the 10% CO and 3% FO 7% CO groups. This suggests that high LA content in CO may represent a threshold for promoting tumour growth whereby further LA content marginally influences additional tumour development. Exposure to the CO n-6 PUFA diet further resulted in earlier onset of puberty compared to the n-3 PUFA-enriched diet containing CO. To investigate the underlying mechanisms, a qPCR analysis of mammary glands and tumour tissue revealed that the n-3 PUFA diets downregulated the expression of pro-tumourigenic immune markers, including CD206 and F4\/80 in the mammary glands and the cannabinoid receptor CB2 in tumours, compared to the n-6 PUFA diets. Conclusions: These findings indicate that the presence of dietary n-3 PUFA plays a key role in modulating mammary tumour development, which may be further influenced by the underlying n-6 PUFA background. The associated changes in immune markers suggest that n-3 PUFA exert anticancer effects in part by shifting the tumour immune microenvironment toward an anti-tumour phenotype and modulating cannabinoid receptor signalling. Collectively, this work informs future human studies investigating the role of dietary fat composition in breast cancer risk.<\/jats:p>","DOI":"10.3390\/nu18040606","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T14:06:16Z","timestamp":1770905176000},"page":"606","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Lifelong n-3 PUFA Consumption Reduces HER2+ Mammary Tumour Growth and Alters Immune Markers Compared to Safflower- or Corn Oil-Based Sources of n-6 PUFA"],"prefix":"10.3390","volume":"18","author":[{"given":"Rahbika","family":"Ashraf","sequence":"first","affiliation":[{"name":"Department of Human Health Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connor D. C.","family":"Buchanan","sequence":"additional","affiliation":[{"name":"Department of Human Health Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyn M.","family":"Hillyer","sequence":"additional","affiliation":[{"name":"Department of Human Health Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizaveta","family":"Ogloblina","sequence":"additional","affiliation":[{"name":"Department of Human Health Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1756-8607","authenticated-orcid":false,"given":"Geoffrey A.","family":"Wood","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard P.","family":"Bazinet","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjeena","family":"Subedi","sequence":"additional","affiliation":[{"name":"School of Mathematics and Statistics, Carleton University, Ottawa, ON K1S 5B6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8230-4926","authenticated-orcid":false,"given":"A. Michelle","family":"Edwards","sequence":"additional","affiliation":[{"name":"Office of Research, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-In","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Muller","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Monk","sequence":"additional","affiliation":[{"name":"Department of Human Health Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay E.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Human Health Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1165-5972","authenticated-orcid":false,"given":"David W. L.","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Human Health Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.breast.2022.08.010","article-title":"Current and future burden of breast cancer: Global statistics for 2020 and 2040","volume":"66","author":"Arnold","year":"2022","journal-title":"Breast"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"\u0141ukasiewicz, S., Czeczelewski, M., Forma, A., Baj, J., Sitarz, R., and Stanis\u0142awek, A. (2021). 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