Tamoxifen and DNA damage/colon cancer?

Rubytoos

I don't want to scare anyone or start some sort of anti-Tamoxifen thread. I was slated to start Tamoxifen and was entirely enthusiastic, but was alerted to some studies that indicate it can cause DNA damage to the colon that can predispose people to colon cancer by as much as 3 fold. Does anyone know anything about this? Is this one of those "one off" studies or is this indeed a risk factor? There is a lot of GI cancer among first degree relatives in my family. I wrote my MO to ask about this and he was dismissive. I was looking into toremifene as an alternative, but there is little information. I really need to take some sort of SERM as AI's are not an alternative for me. Any insight or information will be appreciated.

Pi-Xi

That is chilling. My mother died of colon cancer. I’ve now been diagnosed with basal cell carcinoma. I’d hate to think that tamoxifen further increased my risk. I am now off the drug, but the damage would already have been done.

Wishing you good options.

Beesie

I don't know if there is anything more current - this was published in 2015 - but it provides an analysis of all studies done up to that time.

Risk of Gastric and Colorectal Cancer After Tamoxifen Use for Breast Cancer

https://journals.lww.com/jcge/Abstract/2015/09000/Risk_of_Gastric_and_Colorectal_Cancer_After.9.aspx

"Objective:

It is still controversial whether tamoxifen use for breast cancer will simultaneously cause gastric and colorectal cancer. In this study, we aimed to evaluate the association between tamoxifen use and the risk of gastric and colorectal cancer by performing a systematic review and meta-analysis.

Materials and Methods:

A comprehensive literature search for relevant studies published from 1969 to October 2013 was performed in PubMed, MEDLINE, and ISI Web of Science. Only articles in which gastric and colorectal cancer was reported after tamoxifen therapy for breast cancer were included. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using both the random-effects and fixed-effects models.

Results:

We found a total of 9 studies that met the inclusion criteria for the analysis of tamoxifen use and incidence of gastric and colorectal cancer. Among these studies, 7 were involved with both gastric and colorectal cancer, 1 with gastric cancer and 1 with colorectal cancer. The random-effects model results showed that tamoxifen use for breast cancer was not a risk factor for either gastric cancer (RR=0.92; 95% CI, 0.41-2.07, P=0.84) or colorectal cancer (RR=1.05; 95% CI, 0.90-1.21, P=0.54). Sensitivity analysis indicated that the duration or dose of tamoxifen use had no effect on these 2 gastrointestinal tumors (P>0.05). Stratified analysis showed that tamoxifen use was not associated with the increased risk of gastric and colorectal cancer regardless of whether the latency interval after breast cancer diagnosis was <5 or ≥5 years.

Conclusion:

Our meta-analysis results indicate that there was no substantial increase in gastric and colorectal cancer among the tamoxifen-treated female patients."

Rah2464

Rubytoos my MO told me that breast, skin and colorectal cancers are related and that my risk for colorectal cancer or skin cancer is increased because I have breast cancer, not because of any treatment I take. In fact, as part of my initial workup with her I had to get a colonoscopy as well as a full body skin cancer check. I am on a five year check cycle with the colonoscopy (due to family history) and an annual skin check.

Jelson

Rather than focus on tamoxifen, If I had colon or gastric cancers in my family and was diagnosed with breast cancer, I would seek genetic testing as there are several genetic defects, which though very rare, link breast and other cancers.

Rubytoos

Thank you all for the replies. I appreciate very much the retrospective study and I also appreciate the points made re increased risk and therefore being certain to address that risk, doing check ups. I feel much better about this than I did and honestly feel a SERM for me at least is mega important in terms of overall survival odds.

Beesie--do you have any thoughts re substituting toremifene for tamoxifen? Not sure why I feel it is less risky, but I have that impression. A cousin living in Europe is taking it and as she is on the holy-hell GI cancer side of my family, is the one that alerted me to this concern in the first place. I don't know what DNA adducts are but this was what I read when researching the possible effects of tamoxifene on colon health.

Beesie

Rubytoos, sorry I can't help on the question of toremifene vs. tamoxifen. I never done any reading or searching for information on toremifene so I know nothing about it.

Salamandra

Hi Rubytoos,

I'm taking toremifene after not tolerating tamoxifen. However, my side effects were all immediate and obvious - it's not that I was concerned about long term risks.

There is just less research on toremifene (although I believe the research is still sound enough to feel comfortable using it). That means that there is less evidence of harm. But it's not really easy to know, I think, whether that is because there is less harm or just less evidence.

I think your best bet here is to find doctors that you trust and ask them about their knowledge and research. A great oncologist will know who to ask in the field who knows the most current research, who maybe even is doing the most current research. They know when to bring in which other specialist to consult with about managing risks and co-morbidities. They will be the one who can give you much more solid, informed advice, based on science and your particular case, than you could find here. If you don't have confidence in the first oncologist you consult, look for a second opinion, or a third, etc. I think your research time might be better spent indirectly - researching which oncologists and specialists to ask, rather than directly trying to research these drugs and interactions that professionals take years to build expertise in.

Rubytoos

Salamandra, your point is a good one re toremifene as is your suggestion re going to the right specialist, one willing to at least answer questions or dig further if they don't know. Thanks.