The calpain system is associated with survival of breast cancer patients with large but operable inflammatory and non-inflammatory tumours treated with neoadjuvant chemotherapy

Storr, Sarah J.; Zhang, Siwei; Perren, Tim; Lansdown, Mark; Fatayer, Hiba; Sharma, Nisha; Gahlaut, Renu; Shaaban, Abeer; Martin, Stewart G.

Abstract

The calpains are a family of intracellular cysteine proteases that function in a variety of important cellular functions, including cell signalling, motility, apoptosis and survival. In early invasive breast cancer expression of calpain-1, calpain-2 and their inhibitor, calpastatin, have been associated with clinical outcome and clinicopathological factors.
The expression of calpain-1, calpain-2 and calpastatin was determined using immunohistochemistry on core biopsy samples, in a cohort of large but operable inflammatory and non-inflammatory primary breast cancer patients treated with neoadjuvant chemotherapy. Information on treatment and prognostic variables together with long-term clinical follow-up was available for these patients. Diagnostic pre-chemotherapy core biopsy samples and surgically excised specimens were available for analysis.
Expression of calpastatin, calpain-1 or calpain-2 in the core biopsies was not associated with breast cancer specific survival in the total patient cohort; however, in patients with non-inflammatory breast cancer, high calpastatin expression was significantly associated with adverse breast cancer-specific survival (P=0.035), as was low calpain-2 expression (P=0.031). Low calpastatin expression was significantly associated with adverse breast cancer-specific survival of the inflammatory breast cancer patients (P=0.020), as was low calpain-1 expression (P=0.003).
In conclusion, high calpain-2 and low calpastatin expression is associated with improved breast cancer-specific survival in non-inflammatory large but operable primary breast cancer treated with neoadjuvant chemotherapy. In inflammatory cases, high calpain-1 and high calpastatin expression is associated with improved breast cancer-specific survival. Determining the expression of these proteins may be of clinical relevance. Further validation, in multi-centre cohorts of breast cancer patients treated with neoadjuvant chemotherapy, is warranted.

Citation

Storr, S. J., Zhang, S., Perren, T., Lansdown, M., Fatayer, H., Sharma, N., Gahlaut, R., Shaaban, A., & Martin, S. G. (2016). The calpain system is associated with survival of breast cancer patients with large but operable inflammatory and non-inflammatory tumours treated with neoadjuvant chemotherapy. Oncotarget, 7(30), 47927-47937. https://doi.org/10.18632/oncotarget.10066

• Journal Article Type: Article
• Acceptance Date: May 29, 2016
• Online Publication Date: Jun 15, 2016
• Publication Date: Jun 15, 2016
• Deposit Date: Jun 7, 2016
• Publicly Available Date: Aug 15, 2018
• Journal: Oncotarget
• Electronic ISSN: 1949-2553
• Publisher: Impact Journals
• Peer Reviewed: Peer Reviewed
• Volume: 7
• Issue: 30
• Pages: 47927-47937
• DOI: https://doi.org/10.18632/oncotarget.10066
• Keywords: Calpain; Calpastatin; Breast cancer; Neoadjuvant chemotherapy; Survival
• Public URL: https://nottingham-repository.worktribe.com/output/795086
• Publisher URL: http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5b%5d=10066&author-preview=7rm
• Contract Date: Jun 7, 2016