Page 636 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

614 PART IV Specific Malignancies in the Small Animal Patient

TABLE 28.5 Prognostic Factors and Indication for Adjuvant Chemotherapy with Supporting Level of Evidence in
Dogs with Malignant Mammary Tumors
VetBooks.ir Tumor Size Lymph Node Involvement Histopathologic Type Indication for Evidence Level 1–5 a
Chemotherapy (No or Yes)
<3 cm/40 cc Negative Carcinoma No b 1 140
>3 cm/40 cc Negative Carcinoma Yes c 1, 140 2, 226 4, 227 5 80
Any Positive Carcinoma Yes 3, 13,29,74,77,135,138,143 2, 226 5 80
Any Any Osteosarcoma Yes 3 138,164
Any Any Inflammatory carcinoma Yes 3 101,102,162
a Evidence level 1: Prospective randomized trial; level 2: Prospective, nonrandomized trial; level 3: Retrospective; level 4: Case report(s); level 5: Extrapolation from human breast cancer studies.
b Chemotherapy may be considered if unfavorable histology (vascular invasion or high grade). 134,135,138,139
c Dogs with stage III disease according to the original WHO staging system were included. 226 Stage III disease includes dogs with tumors >5 cm with or without lymph node metastasis. 124

with surgery alone. The use of hormonal therapy in canine therefore the need for more individualized recommendations
MGTs is based on tumor hormone dependence (tumor risk regarding adjuvant care, including whether to perform OHE
and HRs) and the potential to significantly reduce recurrence (one size does not fit all).
and prolong survival in HR-positive cancers similar to human Chemotherapy is often administered to dogs with MGTs
hormonal therapy. This can be achieved by surgical means considered to be at risk for metastasis or recurrence. Most of
(ovariectomy [OVE] or OHE) or medical means, including the evidence regarding the efficacy of adjuvant chemotherapy
specific ER modulators and suppression of estrogen synthesis is weak, but some studies have reported improved outcomes in
by aromatase inhibitors or luteinizing hormone–releasing hor- dogs treated with chemotherapy, alone or in combination with
mone agonists. Tamoxifen, an ER antagonist commonly used nonsteroidal antiinflammatory drugs (NSAIDs) (see Table 28.6).
in women with ER-positive breast cancer, has been evaluated Anthracycline or taxane combinations are considered part of
in dogs both with and without MGTs. Because of the side first-line protocols in human BC in women requiring adjuvant
effects, mostly from proestrogenic signs, this strategy may not therapy 80,156–158 ; however, only inadequately powered nonran-
be tolerable or feasible in dogs. 152,153 Surgical ovarian ablation, domized studies on the efficacy of doxorubicin (DOX), docetaxel,
specifically OVE/OHE, is a more practical solution in the dog. gemcitabine, mitoxantrone, and carboplatin in dogs with high
This will also eliminate the ovarian production of progester- risk or advanced MGTs have been performed and none clearly
one, the other main player in canine mammary tumorigenesis. establish benefit. 150,159–161 Interestingly, NSAIDs, with or without
Alternatively, specific drugs targeting the progesterone receptor chemotherapy, were found to be effective in prolonging survival in
may be considered. A recent randomized study documented dogs with high risk (grade III and/or advanced clinical stage) or
improvements in DFI in specific subset of dogs randomized to inflammatory carcinomas according to several retrospective and
receive a progesterone receptor antagonist (aglepristone) (see prospective studies (see Table 28.6). 102,160,162,163 Chemotherapy
Table 28.6). 154 There are numerous publications on the topic may also have a role in the treatment of primary MG OSA. The
of OHE in canine MGTs. The results are in discordance; most MG is one of the most common sites for extraskeletal OSA and,
of the earlier studies did not report benefit in ovariohyster- according to one small retrospective case series (including primary
ectomized dogs compared with intact dogs. 18,140,141,152,155 A MG OSA and other extraskeletal sites), dogs treated with adjuvant
few of these earlier studies, however, did report benefit; one chemotherapy were significantly less likely to die of tumor-related
study found that the benefit of OHE was only significant in causes than dogs treated with surgery alone. 164
dogs with complex carcinomas. 143 Another study found that Lastly, a prospective randomized trial documented significant
the timing of OHE in relation to tumor surgery was impor- improvement in survival in dogs with histologic grade II or III carci-
165
tant; only dogs with OHE performed within 2 years before or noma treated with perioperative desmopressin. The antimetastatic
concurrently with tumor removal benefited. 148 None of these properties of desmopressin are not fully understood, but it is hypoth-
studies were randomized and the results were not analyzed esized that they in part are mediated through improving hemostasis
in the context of tumor HRs, thus the results must be inter- and preventing cancer cells from gaining access to the vasculature dur-
preted with caution. A recently published prospective random- ing surgical manipulation. 166,167 The results are intriguing, however,
ized study may provide new insight regarding OHE in dogs further confirmatory studies are warranted in light of the fact that
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with mammary carcinoma. As to be expected, no benefit was only two dogs with grade III tumors were randomized to the placebo
noted when all dogs were included in the analysis; however, arm in this particular study and both dogs died shortly after surgery
when the effect of OHE was stratified based on HR positivity, a (MST 35 days). This unusually short survival may contribute to the
modest improvement was noted in dogs that underwent OHE. apparent improvement in survival in the desmopressin arm. As illus-
This difference did not reach significance, likely due to lack trated earlier, there is currently a paucity of high-quality trial evidence
of power. Interestingly, OHE conferred a significant improve- from which to draw information and guidance for treating dogs with
ment in survival in dogs with grade II tumors and dogs that malignant high-risk MGTs. Table 28.5 provides general guidance and
had higher than median peri-surgical serum estradiol, regard- treatment consideration/options and the level of supporting evidence.
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less of ER expression. These results reflect the diversity in Table 28.6 summarizes trials reporting benefit from systemic therapy
the biology and behavior in canine mammary carcinoma and in dogs with MGTs.