Page 638 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

616 PART IV Specific Malignancies in the Small Animal Patient

Hormonal Association
Exposure to ovarian hormones is also strongly implicated in
mammary tumorigenesis in the cat. Sexually intact cats have a
VetBooks.ir 7-fold higher risk than spayed cats. The increased risk in intact
1
Similar to findings
cats has been confirmed by others.
173,176,183
in dogs, exposure from ovarian hormones in cats at an early
age appears crucial. The protective effect of OHE diminishes
quickly over the first few years; risk reductions of 91%, 86%,
and 11% are seen in cats that are ovariohysterectomized before
6 months, between 7 and 12 months, and between 13 and 24
months, respectively. No benefit was found after 24 months. 183
According to the same study, parity did not influence risk for
MGTs.
In addition to endogenous ovarian hormonal influence, expo-
sure to exogenous progestins also increases risk. Cats treated with
progestins have an overall relative risk of 3.4 compared with those
not receiving such treatments, although benign tumors arise more
commonly than malignant tumors (relative risk 5.3 vs 2.8). 173 • Fig. 28.5 Fibroepithelial hyperplasia in a cat. (Courtesy Dr. Lisa Mes-
Unlike dogs, progestin-treated cats were not younger than non- trinho, Faculdade de Medicina Veterinária, Universidade Lusofona de
treated cats when they developed tumors. 173 The tumorigenic Humanidades e Tecnologias, Lisboa, Portugal.)
effects of oral progestins in cats are supported by reports of male
cats with MGTs. MGTs are rare in males, but in a report of 22 analyzing ER in cats. 191 Standardized IHC methods have high
cases, eight (36%) had a history of progestin use. 184 In a recent concordance with DCC methods; 38.5% of the malignant
case series of three male cats with MGTs, all had received mul- tumors and 66.7% of the benign lesions expressed PR accord-
tiple injections of a long-lasting progestin over 5 to 6 years before ing to IHC. 191 In this particular study, sexually intact cats were
tumor development. All had malignant tumors and all devel- more likely to have PR-positive tumors. Lower concordance was
oped subsequent malignant tumors in other glands after initial found between ER analysis by DCC and IHC with IHC being
surgery. 185 Shorter duration of treatment or inconsistent admin- less sensitive than DCC; only 20% of the malignant tumors
istration is less likely to result in malignant tumors, but never- expressed ER according to IHC compared with 44% according
theless induce changes in the MGs. 186 Fibroepithelial hyperplasia to the DCC assay. 191 These results are consistent with other pub-
(fibroadenomatous change, fibroepithelial hypertrophy, mam- lications showing a relatively low ER expression in feline MGTs
mary hypertrophy) is the most common histopathologic change when using IHC.
in cats treated for shorter periods of time and can occur relatively The low HR positivity in the tumors is consistent with the
quickly, even after one injection; however, studies show that regu- higher rate of malignancy and a more aggressive clinical behavior
lar and prolonged administration is needed for malignant tumors in feline MGTs. In contrast to malignant tumors, normal mam-
to develop. 173 mary tissue and dysplastic lesions in the MG express both ER and
PR 72,189,190 ; however, this hormone dependence appears to wane
Tumor Biology: Development, Hormones, with histologic progression from benign to malignant. None of
Growth Factors, and Prognostic Implications the intermediate- or high-grade ductal CIS (nomenclature refer-
ring to breast intraepithelial lesions in women) were ER or PR
The risk for MGT development in cats is determined by expo- positive, 189 whereas the normal and hyperplastic adjacent mam-
sure to ovarian hormones early in life, but the latency period mary tissue expressed HRs. 72,189,190 Fibroepithelial hyperplasia, a
appears long because most cats are older when diagnosed. In progesterone-induced change, has been reported to have high PR
many species, ovarian hormones are necessary for normal MG expression 186 and can be effectively treated by OHE or antipro-
development and maturation, but few studies have examined gestins (Fig. 28.5). 193
hormonal effects on mammary tumorigenesis in cats. The com- In human BC, an inverse relationship between the HR
plex interactions between sex hormones, GH, and IGF-1 have status and HER-2 expression is documented. HER-2 expres-
been discussed in more detail in the section on canine MGTs, sion tends to be higher in cats than in dogs and humans; how-
but progestin-induced mammary production of GH has been ever, a wide range (6%–90%) of HER-2–positive tumors is
documented in the cat. 187,188 It is, however, biologically plau- reported. 194–197
sible that the tumorigenic effects on mammary tissues are simi-
lar across species and that the same general mechanisms are History and Clinical Presentation
involved, specifically sex hormones and GH. Despite ER and
PR expression being implicated in the initial stages of MGT Cats with MGTs are often older and may be sexually intact or
development, many investigators have reported that most feline spayed after they were 2 years old. Tumors are easy to detect
mammary carcinomas are ER and PR negative, although slightly on physical examination and appear as firm discrete mass(es)
more than one-third are PR positive. 72,189–192 The percentage of in the MG(s). One study reported that all glands are equally
ER/PR expression varies between studies and is likely the result susceptible to tumor development, but a later study showed
of differences in case selection, methods, and interpretation of that the cranial glands were less commonly affected. 198,199
the results. The biochemical method, the dextran-coated char- Multiple tumors are common; 60% of cats had more than one
coal (DCC) method, may be more sensitive than IHC when tumor at diagnosis in one report. 174 Careful examination of