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The effect of hormones on the development of canine mammary tumours

Fraser Broadfoot BVetMed MRCVS - 16/07/2017

The effect of hormones on the development of

canine mammary tumours

 

Mammary tumours are one of the most common tumours affecting female dogs1. Around 50%-70% are benign and most carry a favourable prognosis, as long as they have been removed with appropriate surgery2. This article will discuss the effect of hormones on the development of mammary tumours and the implications for prevention and treatment.

 

The reproductive cycle of the bitch is divided into four stages; pro-oestrus and oestrus, which are mediated by oestrogen, dioestrus, which is associated with progesterone and prolactin, and the hormonally quiet period of anoestrus. Unusually, dioestrus has the same length in the pregnant and non-pregnant bitch, which helps to explain the high incidence of pseudopregnancy (or false pregnancy). 

Normal mammary glands contain oestrogen and progesterone receptors3,4 , and these are important for growth and development2. Oestrogen and progesterone, however, are also known to be involved in the pathogenesis and induction of mammary tumours5. This helps to explain why early neutering can reduce the risk of tumours developing later in life, see figure 12. 

Figure 1

Another key hormone is prolactin, which is linked with normal mammary growth and development1,7 and is also essential in maintaining progesterone production during the second two thirds of dioestrus5. Towards the end of dioestrus (around 6-10 weeks after the end of a season) prolactin levels increase further and this results in milk production and nursing behaviour which, if not pregnant, is characteristic of pseudopregnancy.

 

In addition, prolactin has also been shown to have a role in the development of mammary tumours5,7. In a recent study looking at 298 bitches with mammary tumours, 58% were pseudopregnant at initial consultation and 70% had a history of pseudopregnancy. Furthermore, the average age of the pseudopregnanct bitches was 8 +/- 2.5 years, significantly younger than those which were not pseudopregnant (9.1 +/- 2.7 years)8.

 

This relationship between pseudopregnancy and mammary tumours could be explained by the high prolactin and progesterone levels and/or by the hypothesis of Murrell9 which links the increased risk with the prolonged distension of the mammary acini and the stagnation of the milk secretions that favour the local production of carcinogens, tissue hypoxia and the production of free radicals.

 

Figure 2


Pseudopregnancy can be treated with a prolactin inhibitor such as cabergoline (Galastop®: Ceva Animal Health)5. A double-blind placebo controlled trial has also been carried out looking at 96 bitches with concurrent pseudopregnancy and mammary tumours10. After the administration of 7-10 days of cabergoline (at the standard dose) or placebo, the tumours were removed surgically and analysed histologically. In the bitches treated with cabergoline, by contrast with the placebo controls, the following benefits were observed:

  • Improved visualisation – in 12.5% of bitches treated, pre-operative palpation revealed small nodules 0.2-1.3cm in diameter which had not been detected at first consultation (probably hidden by hyperplasia of the mammary gland)
  • Easier surgical procedure – the surgical operation was considered significantly easier with fewer post-operative complications after treatment with cabergoline, due to the reduction in mammary gland engorgement and the prevention of milk  spilling onto the operating area (see figure 2 and 3)
  • Reduction in tumour size – in 23% of cases, several lesions detected before the beginning of treatment had decreased in size (0.7 +/- 0.3cm before treatment, 0.3 +/- 0.15cm after treatment). On histological analysis, the tumours which reacted in this way were found to be benign

 

It is important to note that cabergoline can have hypotensive properties and takes 3-4 days to leave the body. After successful treatment with cabergoline, we therefore recommend waiting one week before carrying out surgery to ensure the drug has left the system and the false pregnancy doesn`t return.

 

Figure 3


To summarise, pseudopregnancy and the hormones oestrogen, progesterone and prolactin can all contribute to the development of mammary tumours. Early neutering can therefore help reduce the risk of mammary glands developing later in life and pseudopregnancy cases can also be treated with a prolactin inhibitor such as cabergoline (Galastop®: Ceva Animal Health). In addition, cabergoline has been shown to be beneficial in the management of dogs with concurrent pesudopregnancy and mammary tumours prior to surgery.

 

 This article was kindly provided by Ceva Animal Health, the makers of Galastop®

 

REFERENCES

1 – Donnay, I. et al. (1994), Influence des antécédents hormonaux sur l’apparition clinique des tumeurs mammaires chez la chienne, Ann. Med. Vet., 138, 109-117.

2 – Murphy, S. (2008), Mammary tumours in dogs and cats, In Practice, 30, 334-339

3 - Donnay, I., et al. (1993) Receptors for estrogens, progesterone and EGF in normal and tumorous mammary tissues, Journal of Reproduction and Fertility, Suppl. 47, 501-512.

4 - Rutterman, G. et al. (1988), Oestrogen and progestin receptors in mammary tissue of the female dog., Br. J. Cancer, 58, 594-599.

5 – Verstegen J. and Onclin-Verstegen K. (2009), Mammary tumours and prolactin, UK Vet, 14, 5.

6 – Ogilvie, G. and Moore, A.S. (2006), Mammary neoplasia. In Managing the Canine Cancer Patient. Trenton, Veterinary Learning Systems. 537-548

7 - Clevenger, C.V. et al. (2003), The role of prolactin in mammary carcinoma. Endocrinology Review, 24, 1-27.

8 - Verstegen, J. et al. (2004), Prolactin, Pseudopregnancy and mammary tumors in the dog, Le Point Veterinaire, 249:44-47

9 - Murrell, T.G.C. (1991) Epidemiological and biochemical support for a theory on the cause and prevention of breast cancer, Med. Hypoth., 36, 389-396.

10 – Verstegen, J. and Onclin, K. (2004), Prolactin, Pseudopregnancy and mammary tumors in the dog, Le Point Veterinaire, 249, 44-47

This article was first published on VetGrad.co.uk in 2014.

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