Sunday Challenge.. Literature Review. Does rituximab cause Breast Cancer?

If ocrelizumab, which depletes CD20 B cells, really causes breast cancer (there were non in the the placebo groups in the trials), then based on biology any long-term depletion of CD20 B cells should cause breast cancer if this is true. 

Was the ocrelizumab a fluke result as we suggests the the result in the cladribine trial was, after looking at the data from other trials with cladribine and the occurrence of cancer in trials with other MS drugs.

Therefore, is it a random fact that is a bit of mud, that can stick do to perceptions, which is supported by another random fact.

So the question is, 

Is there an increased risk of Breast Cancer after Rituximab?.

A quick search on pubmed gives 198 papers. 

If you look… a lot will be using rituximab to treat B lymphoma in the breast. So it needs some detective work. 

I have a date with the DIY paint brush so don’t have the time to do a search but maybe you can just post a list of the papers of what you find in the comments box and we can do a follow-on post with an answer.

I’ll start you off

Fleury I, Chevret S, Pfreundschuh M, Salles G, Coiffier B, van Oers MH, Gisselbrecht C, Zucca E, Herold M, Ghielmini M, Thieblemont C. Rituximab and risk of second primary malignancies in patients with non-Hodgkin lymphoma: a systematic review and meta-analysis.
Ann Oncol. 2016 Mar;27(3):390-7.

Among the 241 solid SPM subtypes reported, 125 occurred in
patients randomized to R and 116 in patients not randomized to
R. High-grade SPM subtypes of solid cancers reported were (in
the order of frequency): lung (R = 18, No R = 16), prostate
(R = 16, No R = 13), colorectal (R = 12, No R = 15), breast
(R = 8, No R = 10)
, pancreas (R = 7, No R = 5), urothelium
(R = 5, No R = 6), melanoma (R = 8, no R = 3), basal cell carcinoma
(R = 7, no R = 3), stomach (R = 3, No R = 6), head and neck
(R = 4, No R = 5), skin cancer not melanoma or basal cell carcinoma
(R = 5, no R = 3), squamous cell (R = 5, No R = 1),
biliary tract (R = 2, No R = 2), esophagus (R = 3, No R = 1), liver
(R = 1, No R = 3), kidney (R = 1, No R = 3), neuroendocrine
(R = 2, No R = 1), endometrium (R = 2, No R = 1), ovary (R = 0,
No R = 2), sarcoma (R = 2, No R = 0), adenocarcinoma of
unknown primary site (R = 2, No R = 0), carcinoma of unknown
primary site (R = 2, No R = 1), thyroid (R = 1, No R = 1), peritoneal
carcinomatosis of unspecified origin (R = 1, No R = 1),
relapsed prostate (R = 0, No R = 1), relapsed breast (R = 0, No
R = 1)
, adrenal metastasis of unspecified origin (R = 0, No
R = 1), anal (R = 0, No R = 1), pleura (R = 1, No R = 0), brain
(R = 0, No R = 1), GIST (R = 0, No R = 1). Low-grade SPM subtypes
consisted of in situ skin cancer or dysplastic naevus (R = 3,
No R = 6), liver adenoma (R = 1, No R = 1), lipoma (R = 1, No
R = 0), meningioma (R = 1, No R = 0), prostate nodule (R = 1,
No R = 0) and chondroma (R = 0, No R = 1)

So there were 8 in the rituximab group and 10 in the non-rituximab group…this could mean neither cause cancer and this is part of life or the both cause breast cancer.

Rituximab trials in other autoimmune diseases would be good place to search.

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  • And were study participants predisposed to breast cancer?

    As much as they deny (they say cases are related to the contraceptive pill with high doses of estrogen), for example, there are several studies that relate the use of oral contraceptives with cases of breast cancer, the longer the use the greater the use risk, and even so the contraceptive pill is forbidden.

  • No takers, then I guess this is an unknown

    I had a quick look at a few trials and there was no mention of cancer. I don't have the time to look maybe someone from a competing company a regulator or someone from Roche has the answer.

  • Neoplastic disorders

    In a 2012 review of trials of chemotherapeutic regimens containing rituximab, therapy-related neoplasms were identified in approximately 4.5% of patients (19 out of 426) within a follow-up period of 44 months [65]. Most cases presented as either acute myeloid leukemia or myelodysplastic syndromes and had often previously achieved at least partial (if not complete) remission. The median survival time was approximately 7 months after diagnosis of the therapy-related neoplasms; however, this was not specific to rituximab, since other agents were a part of the chemotherapeutic regimens.

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