Oral doxycycline is one of the most frequently prescribed medications by optometrists. Doxycycline, a tetracycline derivative and broad-spectrum antibiotic, is commonly used to treat various inflammatory ocular conditions, such as keratoconjunctivitis sicca, meibomitis, rosacea keratitis, corneal ulcers, chlamydial keratoconjunctivitis and recurrent corneal erosion.1-4

Doxycycline also inhibits production of matrix metalloproteinase (MMP), an enzyme that causes collagen destruction.1,2

However, in recent years, there has been discussion about a potential relationship between oral doxycycline and an increased risk for breast cancer. But, is there enough evidence to suggest a positive link?


The Evidence in Favor

Eight years ago, an original study published in the British Journal of Cancer suggested a link between antibacterial medications, such as oral tetracycline and its derivatives, and breast cancer.5 Specifically, this study found that a patients lignan status is markedly reduced by repeated use of antibacterial medications.5 Lignans, a group of antioxidant chemical compounds found in plants, are believed to protect against breast cancer.6

Ultimately, the results were inconclusive, and the authors suggested that other studies are necessary to test and confirm their hypothesis. 

In another study, researchers evaluated the association between breast cancer and antibiotic use in 2.1 million women. At a nine-year follow up, the researchers found that 18,521 women had developed breast cancer.7 The study concluded that use of antibiotics, such as tetracyclines and macrolides, is associated with a slightly increased risk for breast cancer.7

Doxycycline is often used to treat meibomitis, as seen in this patient.

The Evidence Against

However, a literature search uncovered many other studies that show no association between antibiotics and breast cancer incidence.

In fact, several studies conclude that tetracyclines may actually help prevent breast cancer and suppress cancerous cell growth, invasion and metastasis.8

Besides inhibiting MMP activity, oral tetracyclines reduce levels of MMP expression and exhibit selective cytotoxicity toward some of the tumor cell lines.9,10

Specific to breast cancer, research shows that chemically modified tetracycline inhibits secretion of vascular endothelial growth factor (VEGF); this, in turn, restricts tumor invasiveness and metastasis.11

Inhibition of VEGF secretion also halts blood vessel growth, a key factor in cancer progression. New blood vessels directly feed malignant tumors. A study on chicken chorioallantoic membranes during fetal development shows that doxycycline can prevent new blood vessel formation. This suggests that the drug could be used as a potential breast cancer therapy.2

Another study in 2005 showed that doxycycline made anti-tumor medications, such as cyclophosphamide, more effective.12

Studies also show that tetracyclines effectively treat prostate cancer by delaying tumor growth, reducing metastasis and decreasing the incidence of tumors.13
Finally, additional studies have demonstrated that bone metastasis decreased in breast cancer patients who took doxycycline.14,15


The Verdict

Based on the existing research, there is little conclusive evidence to suggest a positive relationship between doxycycline use and an increased risk for breast cancer. Quite the contrary, most documented research concludes that doxycycline may be an effective treatment option for breast cancer.


1. Smith VA, Cook SD. Doxycyclinea role in ocular surface repair. Br J Ophthalmol 2004 May;88(5):619-25.

2. Richardson M, Wong D, Lacroix S, et al. Inhibition by doxycycline of angiogenesis in the chicken chorioallantoic membrane (CAM). Cancer Chemother Pharmacol 2005 Jul;56(1):1-9.

3. Yoo SE, Lee DC, Chang MH. The effect of low dose doxycycline therapy in chronic meibomian gland dysfunction. Korean J Opthalmol 2005 Dec;19(4):258-63.

4. Al-Shehri A, Jastaneiah S, Wagoner MD. Changing trends in the clinical course and outcome of bacterial keratitis at King Khaled Eye Specialist Hospital. Int Ophthalmol 2008 Apr 3 [Epub ahead of print].

5. Knekt P, Adlercreutz H, Rissanen H, et al. Does antibacterial treatment for urinary tract infection contribute to the risk of breast cancer? Br J Cancer 2000 Mar;82(5):1108-10.

6. Amin A, Buratovich M. The Anti-Cancer Charm of Flavonoids: A Cup-of-Tea Will Do! Recent Patents Anticancer Drug Discov 2007 Jun;2(2):109-17.

7. Friedman GD, Oestreicher N, Chan J, et al. Antibiotics and risk of breast cancer: up to 9 years of follow-up of 2.1 million women. Cancer Epidemiol Bio Prev 2006 Nov;15(11):2102-6.

8. Meng Q, Zu J, Goldberg ID, et al. Influence of chemically modified tetracyclines on proliferation, invasion and migration properties of MDA-MB-468 human breast cancer cells. Clin Exp Metastasis 2000;18(2):139-46.

9. Saikali Z, Singh G. Doxycycline and other tetracyclines in the treatment of bone metastasis. Anticancer Drugs 2003 Nov;14 (10)773-8.

10. Gu Y, Lee HM, Roemer EJ, et al. Inhibition of tumor cell invasiveness by chemically modified tetracyclines. Curr Med Chem 2001 Feb;8(3):261-70.

11. Kothari M, Simon SR. Chemically modified tetracyclines inhibit VEGF secretion by breast cancer cell lines. Cytokine 2006 Aug;35(3-4):155-25.

12. Chhipa RR, Singh S, Surve SV, et al. Doxycycline potentiates antitumor effect of cyclophosphamide in mice. Toxicol Appl Pharmacol 2005 Feb;202(3):268-77.

13. Lokeshwar BL, Selzer MG, Zhu BQ, et al. Inhibition of cell proliferation, invasion, tumor growth and metastasis by oral nonantimicrobial tetracycline analog (COL-3) in a metastatic prostate cancer model. Int J Cancer 2002 Mar 10;98(2):297-309.

14. Duivenvoorden WC, Hirte HW, Singh G. Use of tetracycline as an inhibitor of matrix metalloproteinase activity secreted by human bone-metastasizing cancer cells. Invasion Metastasis 1997;17(6):312-22.

15. Duivenvoorden WC, Popovic SV, Lhotak S, et al. Doxycycline decreases tumor burden in a bone metastasis model of human breast cancer. Cancer Res 2002 Mar 15;62(6):1588-91.

Vol. No: 145:08Issue: 8/15/2008