What You Know that Ain’t Necessarily So: Neutering & Mammary Tumors in Dogs

I recently gave a lecture at the Western Veterinary Conference called “What You Know that Ain’t Necessarily So.” The purpose of this was to take some common or controversial beliefs and practices in veterinary medicine and discuss the scientific evidence pertaining to these. This was not intended as a definitive, “final word” on these subjects, but as an illustration of how weak and problematic the evidence often is even behind widely held beliefs. In some cases, these practices or ideas may actually be valid, but without good quality scientific evidence, we should always be cautious and skeptical about them.

Eventually, I will post recordings of the presentations themselves, but for now I am posting a summary of each topic.

Each starts with a focused clinical question using the PICO format.

P– Patient, Problem Define clearly the patient in terms of signalment, health status, and other factors relevant to the treatment, diagnostic test, or other intervention you are considering. Also clearly and narrowly define the problem and any relevant comorbidities. This is a routine part of good clinical practice and so does not represent “extra work” when employed as part of the EBVM process.

I– Intervention Be specific about what you are considering doing, what test, drug, procedure, or other intervention you need information about.

C– Comparator What might you do instead of the intervention you are considering? Nothing is done in isolation, and the value of most of our interventions can only be measured relative to the alternatives. Always remember that educating the client, rather than selling a product or procedure, should often be considered as an alternative to any intervention you are contemplating.

O– Outcome What is the goal of doing something? What, in particular, does the client wish to accomplish. Being clear and explicit, with yourself and the client, about what you are trying to achieve (cure, extended life, improved performance, decreased discomfort, etc.) is essentially in evidence-based practice.

This is then followed by a summary of the evidence available at each of the levels in the following pyramid (which is a pragmatic reinterpretation of the classical pyramid of evidence that is a bit more useful for general practice veterinarians).

Finally, I list the Bottom Line, which is my interpretation of the evidence.

 

Neutering and Mammary Neoplasia in Dogs

1. Clinical question

P- female dogs

I- neutering (timing)

C- remaining intact (timing)

O- incidence/mortality mammary neoplasia

What is Risk in Intact Females?

• 53.3% (varies by breed and age: 4-35/1,000/yr)
  (Moe, 2001)

• 1% 6yrs, 6% 8yrs, 13% 10yrs
• 111/10,000 DYAR (5-319/10,000 DYAR)
  (Egenvall, 2002)

• 205 tumors/100,000 dogs/year SI
  (Dobson, 2002)

2. Synthetic Veterinary Literature

a. One systematic review:

13 peer-reviewed journal articles in English

     9 high risk of bias

     4 moderate risk of bias

          1 found protective association

         2 found no association

         1 found“some protective effect” but no numbers

(Beauvais, 2012)

b. One critically appraised topic

Best Bets for Vets Age at neutering and mammary tumours in bitches

Spaying bitches before the first or second season, or before the age of 2.5 years, may be associated with a reduced risk of developing malignant mammary tumours later in life…However, the evidence is relatively weak, and this should be taken into account alongside other considerations when recommending whether and when to neuter.

3.  Primary Veterinary Literature

• Strong protective effect
• No confidence interval or p-value
• Matched cases/controls, matched analysis?
• Cases/controls from different time periods
• Only for cases with histopathology
• Previous hormone use?

(Schneider, 1969)

• “inconsistent although some protective effect”
• No quantitative assessment
• No control for age, previous hormone use
• Research Beagles
• Neutered at 10-12 years of age
• Primary purpose to evaluate Rad Tx

(Bruenger, 1994)

• No association (neutering & any type of mammary mass)
• Age at neutering not reported
• No control for age, breed, previous hormone use
• Only for cases with histopatholog
• Primary purpose diet and mammary tumors

(Pérez Alenza 1998)

• No association (neutering & proportion of submitted tumor samples neoplastic)
• Age and age at neutering not reported
• No control for age, previous hormone use
• Only for cases with histopathology
• No confidence intervals

(Richards, 2001)

• No association between age at neutering and neoplasia
• All neutered 6 weeks-12 months
• Mammary neoplasia not specifically addressed
• Shelter dogs
• Underpowered for uncommon outcomes

(Spain, 2004)

4. Human Literature- Primary

> 66,000 women studied, observational

The risk for breast cancer was reduced by 27% among women who had hysterectomy and BSO before 45 years of age, and by 20% among those who had simple hysterectomy before age 45 years.

(Gaudet, 2014)

~4,500 women studied, case/control

Bilateral ovariectomy was associated with reduced breast cancer risk overall (odds ratio (OR) = 0.59, 95% confidence interval (CI): 0.50, 0.69) and among women <45 years of age (ORs ranged from 0.31 to 0.52), but not among those who were older at surgery.

(Press, 2011)

Bottom Line–

• Available evidence suggests neutering reduces mammary cancer risk
• Earlier neutering may be more protective
• Great variation with breed, age, other factors
• Existing evidence is very weak
• Strong or numeric claims not justified

Reference

Beauvais W, Cardwell JM, Brodbelt DC. The effect of neutering on the risk of mammary tumours in dogs–a systematic review. J Small Anim Pract. 2012 Jun;53(6):314-22.

Bruenger, FW, et al. Occurrence of mammary-tumors in beagles given RA-226. Radiation Research 1994;138:423-434.

Dobson JM, Samuel S, Milstein H, Rogers K, Wood JL. Canine neoplasia in the UK: estimates of incidence from a population of insured dogs. Journal of Small Animal Practice 2002;43(6);240-6.

Egenvall A, Bonnett BN, Ohagen P, Olson P, Hedhammar A, von Euler H. Incidence of and survival after mammary tumors in a population of over 80,000 insured female dogs in Sweden from 1995 to 2002. Preventative Veterinary Medicine 2002;69:109-27.

Gaudet MM, et al. Obstet Gynecol. Oophorectomy and Hysterectomy and Cancer Incidence in the Cancer Prevention Study-II Nutrition Cohort. 2014:123;1247-1255.

Moe L. Population-based incidence of mammary tumors in some dog breeds. Journal of Reproduction and Fertility 2001;57:439-43.

Pérez Alenza D. et al. Relation between habitual diet and canine mammary tumors in a case-control study. Journal of Veterinary Internal Medicine. 1998;12;132-139.

Press DJ, et al. Breast cancer risk and ovariectomy, hysterectomy, and tubal sterilization in the Women’s Contraceptive and Reproductive Experiences Study. Am J Epidemiol. 2011;173(1):38-47.

Richards HG, et al. An epidemiological analysis of a canine-biopsies database compiled by a diagnostic histopathology service. Preventive Veterinary Medicine. 2001;51:125-136.

Schneider R, Dorn CR, Taylor DO. Factors influencing canine mammary cancer development and postsurgical survival. Journal of the National Cancer Institute 1969;43:1249-61.

Spain CV, Scarlett JM, Houpt KA. Long-term risks and benefits of early-age gonadectomy in dogs. Journal of the American Veterinary Medical Association 2004;224(3):380-7.