Finasteride Use and Breast Cancer in Women

Question:

I read your recent article discussing the risk of breast cancer in spironolactone users. Do women using finasteride place themselves at increased risk of breast cancer?

ANSWER:

Thanks for the question. We received quite a few inquiries last week when I posted this question:

Does Using Spironolactone Increase the Risk of Breast Cancer?

This week, I’d like to address the evidence for another group of antiandrogens known as the 5 alpha reductase inhibitors. This includes finasteride and dutasteride. To date, there is no good evidence to support the notion that use of oral anti-androgens such as finasteride or spironolactone are associated with an increased risk of breast cancer in women either in the general population or in women at increased risk of breast cancer. For finasteride, studies in women have never been done and we rely entirely on studies in males at low risk. For women, only a few studies have looked at breast cancer risks in spironolactone users. These studies have not suggested an increased risk of cancer in spironolactone users who are at low risk for breast cancer. 

 We do not have data on the risk of breast cancer in users of anti-androgens at highest risk. If the patient or her treating physicians feels that her risk of breast cancer may be higher than current estimates then the drug might not be used given that we have no information about the risks in these high risk groups.  I will first address what is known at present about the risk of breast cancer from finasteride and then address how a patient may come to get a better estimate of risk.  References for all the studies discussed are provided at the end.

 

Finasteride and Breast Cancer Risk: No studies in Women

For finasteride-related risk, the best means we have in the present day of addressing this question is by looking at the risk of breast cancer in men using finasteride and extrapolating the data the best we can to estimate the potential risk in female users.  We do not have studies in women. Male breast cancer is a rare condition with a lifetime risk of 0.1 %. In men, its behavior is similar to breast carcinoma in postmenopausal women.  So while studying male breast cancer and extrapolating the information to female breast cancer is not ideal, it is the best method we have in the present day.

There have been case reports and clinical trial results that suggested that treatment with 5ARIs may be associated with male breast cancer. Most studies to date however, suggest that it is not. All data needs to be taken into context with all available data to date. It should be noted that a warning label has been placed on finasteride packaging in many countries until this issue is further evaluated. An evidence review by the United Kingdom’s (UK) national drug agency resulted in a finasteride drug warning label for breast cancer in the UK and Canada and initiation of an FDA safety probe for all 5ARIs in 2010.

 

It is impossible to ascertain risk of cancer from the original short duration clinical trials. In other words, one is not going to get a sense of the risk of breast cancer by looking up a journal article about a 1 or 2 year study with finasteride. It’s far too short of a period. This is because such typical clinical trials are neither large enough nor have long enough follow-up to identify male breast cancer cases in men who use finasteride. The best type of studies we have at present are observational studies where men with breast cancer are compared to men without breast cancer. Such “case-control studies” are an invaluable tool to assess this important question. I will review many such case control studies below. 

 

A. 2016-2018 PUBLISHED STUDIES ON FINASTERIDE AND BREAST CANCER IN MEN

 

Meijer and colleagues recently assessed the possible relationship between finasteride and breast cancer by combining nationwide registers in 4 countries (Denmark, Finland, Norway, and Sweden) to assess the potential association between finasteride and male breast cancer.  A cohort of all males with dispensed finasteride (1,365,088 person years) was followed up for up to 15 years for breast cancer, and compared to a cohort of males not receiving finasteride.  An increased risk of male breast cancer was found among finasteride users (IRR = 1.44, 95% confidence interval [95% CI] = 1.11-1.88) compared to nonusers.  The analyses suggested possible ascertainment bias and did not support a clear relationship between dispensed finasteride and male breast cancer.  

Hagberg et al conducted a cohort study with nested case–control analyses using the UK Clinical Practice Research Datalink. 5ARI users did not have an increased risk of breast cancer compared to unexposed men (OR=1.52, 95% CI 0.61–3.80).

 

B. 2013-2015 PUBLISHED STUDIESON FINASTERIDE AND BREAST CANCER IN MEN

In 2014, Duijnhoven and colleagues in the Netherlands performed acase-control study with data from the United Kingdom Clinical Practice Research Datalink database among all men aged 45 years and older. Cases of men diagnosed with breast cancer were matched to up 10 controls. There were 398 cases were identified and matched to 3,930 controls. The “ever use” of 5-ARIs was associated with an adjusted odds ratio for breast cancer of 1.08 (95 % CI 0.62-1.87) compared to non-users. Increasing cumulative duration of treatment showed no increasing risks. The conclusion here in Duijnhoven’s study was that there was no evidence of an association between short- or long-term treatment with 5-ARIs and the risk for breast cancer in older men.

In 2013, Bird and colleagues in the United States published a cased control study of men age 40 to 85 years old. Here there were 339 breast cancer cases matched to 6,780 controls. There were no statistically significant associations observed between 5α-reductase inhibitors and breast cancer regardless of exposure assessment. Their conclusion was that the lack of an association in our study suggests that the development of breast cancer should not influence the prescribing of 5α-reductase inhibitor therapy.

 

C. 2003-2012 PUBLISHED STUDIESON FINASTERIDE AND BREAST CANCER IN MEN

In the 2003 PCPT study, Thompson and colleagues published data on 18882 men aged 55 years or older who were randomized to treatment with 5 mg/day finasteride (n = 9423) or placebo (n = 9459) for 7 years. One case of breast cancer was reported as an adverse experience in each treatment group during the study.  In this very large long-term study, an increased incidence of breast cancer in the finasteride group compared to placebo was not observed.

The main study that drew attention to a potential relationship between finasteride and breast cancer was a 2003 study by McConnell. In this study, 3047 patients were randomized to a double-blind, multi-center, placebo-controlled clinical trial for 4-6 years. The 4 different patient groups were administered different drugs: placebo; 8 mg doxazosin; 5 mg finasteride and a combination of 8 mg doxazosin and 5 mg finasteride. Three cases of breast cancer occurred in the finasteride-treated group and 1 case of breast cancer occurred in the combination group. No predisposing factors were identified. Duration of treatment ranged from 1.8 years to 5 years. The occurrence of 4 cases of breast cancer in 3047 patients was considered high considering the normal incidence in the general population of 1 case in 100,000 man-years. Treatment with finasteride appeared in this study to confer 200-fold risk for breast cancer in comparison to patients not receiving the drug.

 

D. 1996-2002 PUBLISHED STUDIES ON FINASTERIDE AND BREAST CANCER IN MEN

 

In 1996, Prescription Event Monitoring (PEM) Study was published. This study was conducted by Drug Safety Research Unit (DSRU) and involved a total of 14,772 patients (mostly male) under observation of General Practitioners from 1992–1994. There were 2 reported breast carcinomas. For one of the events, the time to onset from commencement of finasteride treatment was recorded as 5 months, the other was unknown. The PEM study in 1996 concluded overall that that finasteride is acceptably safe when used in accordance with the current prescribing information.However, it is not possible from this study to evaluate the cases of breast cancer and their causal relationship with finasteride, as enough data is not available regarding the 2 events of breast carcinoma.

 

In 1998, McConnell and colleagues published the Proscar long term efficacy and safety study (PLESS). There were 3040 patients were followed up for a period of 4 years. The patients were randomized in approximately equal proportions to receive either 5 mg finasteride or placebo for up to 4 years. In this study, there were no cases of male breast cancer reported in finasteride-treated subjects, and 2 cases were reported in placebo-treated subjects.

Summary and Conclusion

The evidence to date does not point to an association between finasteride or dutasteride use and breast cancer in women at low risk. It is absolutely critical to keep in mind that the studies I have mentioned above above were conducted in men with low risk of breast cancer and not in women (and not in women who have high baseline risks of breast cancer and not in women who already have breast cancer). Also most of the studies have looked at finasteride rather than dutasteride but of course some of the studies looked collectively at both types of alpha reductase inhibitors. This is important to keep in mind. Many physicians continue to avoid avoid prescribing any type of anti androgen to patients with a history of breast cancer (or at highest risk of breast cancer) given that no such studies have been done. However, for most women, there is no evidence to suggest that their use of finasteride or dutasteride increases their risk of developing breast cancer.

REFERENCES

 

1.    Hagberg KW, et al. Risk of gynecomastia and breast cancer associated with the use of 5-alpha reductase inhibitors for benign prostatic hyperplasia. Clin Epidemiol. 2017.

2.     Wiebe JP, et al. Progesterone-induced stimulation of mammary tumorigenesis is due to the progesterone metabolite, 5α-dihydroprogesterone (5αP) and can be suppressed by the 5α-reductase inhibitor, finasteride. J Steroid Biochem Mol Biol. 2015.

3.     Meijer M, et al.  Finasteride treatment and male breast cancer: a register-based cohort study in four Nordic countries. Cancer Med. 2018.

4.     Duijnhoven RG, et al. Long-term use of 5α-reductase inhibitors and the risk of male breast cancer. Cancer Causes Control. 2014.

5.    Bird ST, et al. Male breast cancer and 5α-reductase inhibitors finasteride and dutasteride.

J Urol. 2013.

6.    McConnell JD, Bruskewitz R, Walsh P, Andriole G, Lieber M, Holtgrewe HL, et al. The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. N Engl J Med. 1998;338:557–63.  

 

7.    McConnell JD, Roehrborn CG, Bautista OM, Andriole GL, Jr, Dixon CM, Kusek JW, et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Eng J Med. 2003;349:2387–98 

8.    Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, et al. The Influence of finasteride on the development of prostate cancer. N Engl J Med. 2003;349:215–24.

9.    Wilton L, Pearce G, Edet E, Freemantle S, Stephens sMD, Mann RD. The safety of finasteride used in benign prostatic hypertrophy: a non-interventional observational cohort study in 14,772 patients. Br J Urol. 1996;78:379–84.  

10.  Mackenzie IS, et al. Spironolactone use and risk of incident cancers: a retrospective, matched cohort study. Br J Clin Pharmacol. 2017.

11. Biggar RJ, et al. Spironolactone use and the risk of breast and gynecologic cancers. Cancer Epidemiol. 2013.

12.  Mackenzie IS, et al. Spironolactone and risk of incident breast cancer in women older than 55 years: retrospective, matched cohort study. BMJ. 2012.




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