Genetic welfare problems of companion animals

 

Mammary Tumours   

 

Breed: English Cocker Spaniel (ECS)

 

Condition:  Mammary Tumours

Related terms: mammary cancer; mammary adenocarcinoma; mammary carcinoma, mammary adenoma, mixed mammary tumour; inflammatory mammary carcinoma; mammary sarcoma; mammary carcinoma; mammary carcinosarcoma.

Outline: English Cocker spaniels are particularly predisposed to mammary tumours. About 30% of these tumours are malignant and, unless promptly diagnosed and successfully treated, they have a progressively serious effect on welfare. Their effects cause malaise, weight loss, inappetance, pain and discomfort and lead to the death of the animal.

 


 

Summary of Information

(for more information click on the links below)

 

 

1.           Brief description

Mammary gland tumours (MTs) are common, accounting for about half of all tumours (cancers) in female dogs (Egenvall et al 2005, Moe 2001). They can be benign or malignant; in the latter case, showing invasion of local tissue and spread to other sites in the affected animal’s body. English Cocker spaniels are known to be particularly predisposed to these tumours (Henry 2009, Zatloukal et al 2005, Moe 2001, Cohen et al 1974, Mitchell et al 1974), being about twice as likely to develop malignant mammary tumours as the average dog (Zatloukal et al 2005).

The clinical signs and the prognosis vary hugely depending on the type of the tumour and the stage of progression (if malignant). It is common for MTs to first be identified by attentive owners, as lumps in the mammary tissue, or by a vet during routine veterinary checks or examinations for other problems.

 

Benign tumours cause few problems unless they become large enough that the skin covering them becomes damaged and ulcerated. They then may become sore and infected. The dog may lick the area frequently and there may be a pusy discharge and an unpleasant smell. If the tumour becomes very large, it may interfere with the animal’s normal movement.

 

The signs caused by malignant tumours depend both on their effects at the local site and the location of any secondary metastases. At the local site, they may become ulcerated, causing the signs outlined above for ulcerated, benign tumours. The most common site for secondary metastases, in which the tumour spreads to other parts of the body through the blood or lymphatic circulations, is the lungs, but these malignant tumours may occur elsewhere (Murphy 2008, Henry 2009). As they spread to other parts of the body, signs of disease develop due to the damage they cause to other organs and tissues. The dogs will generally show increasing depression associated with malaise and pain and will lose weight and appetite. Breathing problems may occur if the lungs are affected.

The prognosis for these dogs with MTs (as for other breeds) is generally good, if the tumours are detected early and if surgical removal is successful, but some malignant tumours carry a much poorer prognosis.

 

2.           Intensity of welfare impact             

The welfare effects of these tumours is very variable, from little impact if the cancer mass is small and benign, through to life-threatening illness with pain and discomfort if the mass or masses are large and malignant. The tumours can cause distress, weakness, feelings of illness, inappetance and lead to difficulty in breathing. They can therefore have a very serious effect on the dog’s quality of life.

Treatment for the tumours may include surgery, pain-relieving medications, chemotherapy, hormonal therapies and radiation. Such treatments can themselves have significant adverse welfare impacts as they necessitate regular visits to the vets, which may be stressful, and some can have significant adverse side-effects.

 

3.           Duration of welfare impact

 

Dogs affected with this condition usually first develop it when they are middle-aged or older. In cases in which these tumours affect welfare, the time course of the disease can be long; with untreated tumours causing progressive disease over months, leading eventually to the death of the affected animal. The time course of treatments can also be prolonged.

 

4.           Number of animals affected

 

Mammary tumours are known to be common in female dogs, accounting for about half of all tumours, of which approximately 50%are malignant (Gilbertson et al 1983, Moulton et al 1970). English Cocker spaniels are known to be particularly predisposed to developing tumours (Henry 2009, Zatloukal et al 2005, Moe 2001, Cohen et al 1974, Mitchell et al 1974) and it has been suggested that they are twice as likely as the average dog to suffer from malignant mammary tumours (Zatloukal et al 2005). However, we are unaware of any specific data on the prevalence of these tumours in this breed.

 

5.           Diagnosis

The diagnosis of a mammary tumour needs to be confirmed by microscopic examination of any tissue biopsies taken from lumps found. Biopsies from nearby lymph nodes and radiographs (x-rays) of the lungs can help in assessing the developmental stage of the tumour and in identifying metastatic spread.

 

6.           Genetics

 

There is good evidence that the predisposition to mammary tumours in this breed has a polygenic basis (ie it is due to more than one gene) and that environmental factors may also play a role.


7.           How do you know if an animal is a carrier or likely to become affected?

Currently it is not possible to identify carrier individuals, ie those that may pass on the genetic predisposition to the disease without developing it themselves, or those which are likely to go on to develop it themselves.

 

8.          Methods and prospects for elimination of the problem

 

We are unaware of any breeding programs aimed at reducing the prevalence of mammary tumours in any breed. As with other complex, multi-gene diseases, in which environmental factors also play a part, good progress in reducing the prevalence of this disease is likely to be aided by greater knowledge of the underlying genetics and the development of genetic tests to identify those individuals that are at high risk of developing the disease, or which may carry the genes, prior to breeding age.

 

 


 

For further details about this condition, please click on the following:

 

 

 

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1.           Clinical and pathological effects

 

Mammary tumours (MTs) are one of the commonest tumours (cancers) affecting female dogs, accounting for about half of all tumours in them (Egenvall et al 2005, Moe 2001). Male dogs account for only 1% of cases of the disease (Murphy 2008).

Dogs usually have five pairs of mammary glands, running in two rows either side of the midline of the abdomen. There are two cranial/thoracic pairs (those nearest the dog’s head), two abdominal pairs and one caudal/inguinal pair (those nearest to the tail).

Tumours are categorised on the basis of where they primarily (first) develop (and for this condition we are discussing only primary mammary gland tumours – those that first arise in these glands) and on the basis of the cell type that they arise from. Several types of primary tumours can develop in the mammary glands of dogs (see below).

Tumours are also categorised on the basis of their behaviour: whether they are benign – growing bigger in the local area but not invading surrounding tissue or spreading elsewhere in the body, or malignant - growing into, invading, and damaging the tissues that surround them and spreading, via the blood stream or lymphatic system, to distant parts of the body. The level of malignancy can be assessed by examination of the cells under the microscope to identify the type of cell they derive from, how rapidly they appear to be dividing, and the damage they are causing to surrounding tissue.

Cells become cancerous because of damage to their DNA (deoxyribonucleic acid) such that the cells become abnormal in structure and function. The causes of this genetic damage are varied. There may be an inherited trait that makes the cells more prone to such changes, or it may follow damage to the DNA by environmental factors either from within the body (such as abnormal hormone levels) or by external factors.

Whilst the causes of mammary tumours are not fully understood, the various risk factors listed below are thought to play a role:

  • Genetic factors are considered to play a major role, underlying specific breed predispositions to developing the disease, as in English Cocker spaniels (Henry 2009).
  • Exposure to female reproductive hormones is known to be another important factor. Normal mammary tissue contains receptors for the female hormones oestrogen and progesterone and their production during puberty influences the growth and development of mammary tissue in female dogs. The age at which neutering occurs can affect the risk of developing mammary tumours because neutering female dogs involves the removal of the ovaries, which are the main sources of these female hormones. If bitches are neutered prior to the first oestrus cycle (ie prior to puberty) the lifetime risk of developing mammary tumours is 0.05% compared to a 26% risk if the bitch is not neutered until after her second oestrus cycle (Ogilvie & Moore 2006). Giving progesterone-like hormones to manipulate the reproductive cycles in bitches has also been shown to increase the risk of these tumours (Murphy 2008). Oestrogen-producing tumours can be a cause of the rare cases of male mammary tumours (Henry 2009).
  • Obesity when young has been shown to increase risk of these tumours (Perez Alenza et al 1998, Perez Alenza et al 2000).
  • Feeding home made diets, especially those rich in red meats, appears to increase the risk of tumours compared to feeding commercial foods (Perez Alenza et al 2000).

 

It has been suggested that about 50% of mammary tumours in dogs are benign but surveys may be biased because benign growths tend not to be investigated. A more accurate figure of the proportion that are benign therefore may be nearer 70% (Murphy 2008). Those classified as malignant have a range of clinical malignancies.

 

Using the classification of the World Health Organisation as presented by Murphy (2008), the types of malignant mammary tumour that occur in dogs include the following.

  • Carcinoma in situ - this form of mammary tumour is very superficial and unlikely to metastasise
  • Complex carcinoma – this is a common form. About 10% of this type spread via the lymphatic system
  • Simple carcinoma including tubulopapillary carcinoma, solid or anaplastic types – these are the most common group of malignant mammary tumours, with the anaplastic type being most likely to metastase.
  • Special types of carcinoma including spindle cell, squamous cell, mucinous and lipid-rich. These are rare. The squamous cell carcinoma is the most likely of the group to spread elsewhere in the body.
  • Sarcoma– including fibrosarcoma, osteosarcoma and others. Bitches with these forms have a poor prognosis as these tumours are likely to reoccur locally after surgical removal, and to metastasise. They constitute 10 to 15% of all malignant mammary tumours.Carcinosarcoma – These are formed of mixtures of different tumour cell types.
  • Carcinoma or sarcoma in benign tumour

 

Benign forms of mammary tumour include adenoma, fibroadenoma and benign mixed (made up of a variety of different cell types) (Murphy 2008).

 

Malignant tumours are also classified according to their clinical stage ie on the basis of the extent of tumour invasion of the surrounding tissues and of spread to distant sites.

 

It is common for dogs to have more than one tumour present. Henry (2009) suggested that over 50% of affected dogs have more than one mass present at veterinary examination. The different lumps or masses may or may not be all of the same tumour type.

 

It is common for these tumours to first be identified by attentive owners, as lumps in the mammary tissue, or by vets undertaking routine checks or during examinations for other problems. The clinical signs and the prognosis vary greatly depending on the type of tumour present and its stage of progression.

 

Benign tumours cause few problems, unless they are large enough to cause the overlying skin to become damaged and ulcerated. They then may become sore and infected and the dog may lick the area frequently. There may be a pusy discharge and an unpleasant smell. If the tumour becomes very large it may interfere with the animal’s normal movement.

 

The signs caused by malignant tumours depend both on their effects at the local site and the location of any secondary metastases. At the local site, they may become ulcerated, causing the signs outlined above for ulcerated, benign tumours. The most common site for secondary metastases, in which the tumour spreads to other parts of the body through the blood or lymphatic circulations, is the lungs, but these malignant tumours may occur elsewhere (Murphy 2008, Henry 2009). As they spread to other parts of the body, signs of disease develop due to the damage they cause to other organs and tissues. The dogs will generally show increasing depression associated with malaise and pain and will lose weight and appetite. Breathing problems may occur if the lungs are affected.

 

Inflammatory carcinomas are a subtype of malignant mammary tumours which present with very different signs compared with other forms (Murphy 2008). They can be confused with mastitis (inflammation and infection of the mammary glands) as the affected glands are hot, swollen and painful. The skin over the glands may be inflamed, having vesicles and pustules (blisters and spots) and the affected dog’s limbs may also be swollen (Murphy 2008). Between 4% and 18% of malignant mammary tumours are of this inflammatory carcinoma type (Reiman no date; http://www.vsso.org/Mammary_Tumors_-_Canine.html), but they are more often seen in larger breeds rather than in Cocker spaniels. The prognosis (future outlook) for bitches with inflammatory carcinomas is very poor (Murphy 2008).

The prognosis for other bitches with other forms of mammary tumours is generally much better, if the tumours are identified early and if appropriate surgical removal is undertaken (Murphy 2008). Surgical removal is the most effective method of treatment of mammary tumours, except for inflammatory carcinomas for which surgery is contraindicated (Murphy 2008; Henry 2009). Ovariohysterectomy (removal of the ovaries and uterus) as an adjunct therapy to tumour removal has been shown to increase survival times (Sorenmo et al 2000; Chang et al 2005). Chemotherapy, hormonal therapy and radiation are sometimes used as adjunct therapies following surgery but their benefits have yet to be fully proven (Henry 2009).

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2.               Intensity of welfare impact

The welfare effects of these tumours are extremely variable depending on the type of tumour present and the stage of the disease. Benign tumours cause little or no problem, unless their size causes movement restrictions or soreness and irritation due to ulceration of overlying skin. Malignant tumours progressively cause more severe impacts (unless surgically removed before metastasis has occurred). Metastases in the lungs can lead to distress due to respiratory compromise and to increasing difficulty with breathing. The effects of metastases elsewhere in the body depend on which tissues they damage but may generally, in time, lead to the affected animal feeling ill, to lack energy and appetite and to suffer discomfort and pain. They may develop uncomfortable swelling of limbs. Local tumour growth and spread can lead to ulceration with accompanying discomfort and pain.

Inflammatory carcinoma cause severe discomfort and pain which needs palliative control with drugs (Murphy 2008). Affected bitches may feel weak, inappetant and ill. In these, and in other cases with progressive malignant tumours, euthanasia may be necessary to relieve suffering.

Treatments can themselves have adverse welfare effects. Some dogs may be stressed by repeated visits for veterinary treatment and treatments may involve major surgery, regular hormonal therapy or injections of chemotherapeutic agents. Some chemotherapeutic drugs have significant adverse side effects which affect welfare: eg doxorubicin can exacerbate heart conditions (ie make them worse). Some pain relieving medications can also have significant welfare effects through side effects such as gut irritation.


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3.           Duration of welfare impact

 

Mammary tumours mostly occur in middle-aged or older dogs, the average age at diagnosis being ten to eleven years (Murphy 2008). Many affected dogs may have developed tumours many months prior to their detection, as, in the early stages, they cause few problems. The mean survival time for dogs with malignant mammary tumours was reported by Henry (2009) to be 70 weeks from surgery (Henry 2009). During this period the welfare impacts of the condition may vary among animals, with some being free of clinical signs for months. Those with severe metastasis will suffer progressively serious welfare effects in the months between surgery and their death or euthanasia.



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4.           Number of animals affected

 

English Cocker spaniels are known to be particularly predisposed to develop mammary tumours (Henry 2009, Zatloukal et al 2005, Moe 2001, Cohen et al 1974, Mitchell et al 1974). In the past it has been suggested that, taking dogs of all breeds together, up to 26% of un-spayed bitches or those spayed after the age of two years were likely to develop these tumours (Schneider et al 1969). Recently, in the USA, the prevalence of mammary tumours in the dog population as a whole has been suggested to be 200 cases per 100,000 dogs ie 0.2% of the population (Henry 2009). In Sweden, 111 cases were found per 10,000 dog-years at risk in the insured population studied by Egenvall et al (2005). Zatloukal and others (2005) found English Cocker Spaniels to have a 2.1 times greater risk of developing mammary tumours than the average for all dogs. If the overall prevalence rate in un-spayed bitches (taking all breeds together) is 26%, and English Cocker spaniels are twice as likely to develop this disease than the average across breeds; this suggests that the prevalence may be about 50% in un-spayed female English Cocker spaniels. However, we are unaware of any specific surveys on the prevalence of these tumours in English Cocker Spaniels.

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5.           Diagnosis

 

A tumour may be suspected when an abnormal lump is felt within the mammary glands. The diagnosis is confirmed by microscopic examination of any tissue biopsies taken from lumps found. Chest radiographs (x-rays) and biopsies from nearby lymph nodes may taken to help assess the stage of the tumour and to identify any metastatic spread.

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6.           Genetics

The strong breed associated risk of mammary tumours in English Cocker spaniels is highly suggestive of a genetic cause or causes in these dogs (Borge et al 2011). This breed is reported to be particularly predisposed to the disease (Henry 2009, Zatloukal et al 2005, Moe 2001, Cohen et al 1974, Mitchell et al 1974). It is thought that several genes, as well as environmental factors, are likely to be involved in the its development (http://www.vet.cam.ac.uk/idid/detail.php?record=1454; Rivera 2010) but this has yet to be fully confirmed. Two genes, BRCA1 and BRCA2 -known to be important risk factors for the development of breast cancer in humans, have been shown to significantly increase the risk of developing mammary tumours in a closely related breed, the English Springer spaniel (Rivera et al 2009), and another gene has been shown to provide protection against the disease in the same breed (Rivera 2010).

 
 

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7.           How do you know if an animal is a carrier or likely to become affected?

Currently it is not possible to know which dogs will develop the condition. It is likely that affected puppies can be born to unaffected parents. Determining carriers - those which carry and may pass on the genes but which do not show signs of the disease themselves - is not presently possible. Affected individuals are likely to identified only well after they have reached breeding age.


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8.          Methods and prospects for elimination of the problem

We are unaware of any breeding programs aimed at reducing the prevalence of mammary tumours in any breed. As with other complex, multi-gene diseases, in which environmental factors also play a part, good progress in reducing the prevalence of this disease is likely to be aided by greater knowledge of the underlying genetics and the development of genetic tests to identify those individuals that are at high risk of developing the disease, or which may carry the genes, prior to breeding age.

Like other complex, multi-gene diseases in which environmental factors also play a part, good progress in reducing the prevalence of CMT is likely to be aided by greater knowledge of the underlying genetics and the development of genetic tests to identify those individuals that are at high risk of developing the disease, or which may carry the genes, prior to breeding age. Work is currently underway at the Animal Health Trust in the UK and elsewhere to investigate the genetic basis of mammary tumours in English Cocker spaniels and other commonly affected breeds (http://www.theCockerspanielclub.co.uk/health.htm, Rivera 2010).

One approach recommended for controlling suspected complex, polygenic conditions is to breed from dogs that have a better breeding value (see below) than average for the breed (Bell 2010). Breeding value takes account the chances of the disease occurring in both the individual being evaluated and its relatives (ie siblings, parents, grandparents and earlier relatives). In estimating breeding value, the genetic health of these individuals is compared to the average for the breed. This approach could possibly be used to tackle the high prevalence of mammary tumours in these spaniels if extensive breed lineage and ancestor health data are available. Out-breeding these dogs with those of breeds known to have a much lower prevalence of mammary tumours may lead to a decreasing incidence of the disease.

 

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9.          Acknowledgements

UFAW is grateful to Rosie Godfrey BVetMed MRCVS and David Godfrey BVetMed FRCVS for their work in compiling this section and to Dr James Yeates for his contribution.

 

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10.          References

Bell JS (2010) Genetic Testing and Genetic Counseling in Pet and Breeding Dogs. 35th World Small Animal Veterinary Association World Congress Proceedings. 2-5th June 2010, Geneva, Switzerland. http://www.vin.com/Members/Proceedings/Proceedings.plx?CID=wsava2010&PID=pr56159&O=VIN accessed 19.8.2011

 

BorgeKS, Børresen-Dale AL and Lingass F (2011) Identification of genetic variation in 11 candidate genes of canine mammary tumour. Veterinary and Comparative Oncology. doi: 10.1111/j.1476-5829.2010.00250.x

 

ChangSC, Chang CC, Chang TJ and Wong ML (2005) Prognostic factors associated with survival two years after surgery in dogs with malignant mammary tumors: 79 cases. Journal of American Veterinary Medicine Association 227: 1625-1929

Cohen D, Reif JS, Brodey RS and Keiser H (1974) Epidemiological analysis of the most prevalent sites and types of canine neoplasia observed in a veterinary hospital. Cancer Research 34: 2859-2868

 

Egenvall A, Bonnett BN, Ohagen P, Olson P, Hedhammar A and von Euler H (2005) Incidence of and survival after mammary tumors in a population of over 80,000 insured female dogs in Sweden from 1995 to 2002. Preventive Veterinary Medicine 69: 109-27

 

Gilbertson SR, Kurzman ID, Zachrau RE, Hurvitz AI and Black MM (1983) Canine mammary epithelial neoplasms: biologic implications of morphologic characteristics assessed in 232 dogs. Veterinary Pathology 20: 127-42

 

Henry CJ (2009) Mammary Cancer in Bongura J and Twedt D (eds) Kirks Current Veterinary Therapy XIV p 363. Saunders Elsevier, St. Louis, MissouriUSA

 

Mitchell L, De la Iglesia FA, Wenkoff MS, van Dreumel AA and Lumb G (1974) Mammary tumors in dogs: Survey of clinical and pathological characteristics. Canadian Veterinary Journal 15: 131-138

 

Moe L (2001) Population-based incidence of mammary tumours in some dog breeds. Journal of Reproduction and Fertility Supplement 57: 439-443

 

Moulton JE, Taylor DO, Dorn CR and Andersen AC (1970) Canine mammary tumors. Veterinary Pathology 7(4): 289-320

 

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

 

Ogilvie G and Moore AS (Eds) (2006) Mammary neoplasia. In Managing the Canine Cancer Patient. Trenton, Veterinary Learning Systems. pp 537-548

 

Perez Alenza D, Rutteman GR, Peña L, Beynen AC and Cuesta P (1998) Relation between habitual diet and canine mammary tumors in a case-control study. Journal of Veterinary

Internal Medicine 12: 132-139

 

Perez Alenza MD, Peña L, del Castillo Nand Nieto AI (2000) Factors influencing the incidence and prognosis of canine mammary tumours. Journal of Small Animal Practice 41(7): 287-91

 

Reiman R no date Canine Mammary Tumors. www.animalemergencycenter.com/.../CANINE_MAMMARY_TUMORS.pdf. Accessed 1.9.11

 

Rivera P (2010) Biochemical Markers and Genetic Risk Factors in Canine Tumors. Doctoral ThesisSwedishUniversity of Agricultural Sciences, Uppsala. www.diss-epsilon.slu.se:8080/archive/00002280/01/rivera_p_100503.pdf. Accessed 29.8.11

 

Rivera P, Melin M, Biagi T, Fall T, Häggström J, Lindblad-Toh K and von Euler H (2009) Mammary tumor development in dogs is associated with BRCA1 and BRCA2. Cancer Research 69: 8770-8774

 

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

 

Sorenmo KU, Shofer FS and Goldschmidt MH (2000) Effect of spaying and timing of spaying on survival of dogs with mammary carcinoma. Journal of Veterinary Internal Medicine 14: 266-270

Zatloukal J, Lorenzová J, Tich F, Neâas A, Kecová H and Kohout P (2005) Breed and Age as Risk Factors for Canine Mammary Tumours. Acta Vet Brno 74: 103-109

 

http://www.theCockerspanielclub.co.uk/health.htm

 

http://www.vet.cam.ac.uk/idid/detail.php?record=1454

 

http://www.vsso.org/Mammary_Tumors_-_Canine.html. Accessed 2.9.11

 

 

 

 

 

© UFAW 2011

 

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