Mammary Gland Flashcards
What are the 3 main factors for mammary gland tumour development in dogs?
- age (younger tend to be benign)
- hormonal exposure
- breed
How does the number of estrous cycle affect the risk of mammary gland tumour?
If OHE is done
- before the 1st estrous: risk of MGT is 0.5%
- before the 2nd estrous: 8%
- before the 3rd estrous: 26%
- However, doing OHE at the time of MGT removal is still beneficial at reducing the risk of further MGT development
- the use of progestin can increase the risk of (benign) MGT; combination of estrogen and progestin –> more likely to have malignant MGT
Which breeds appear to be predisposed to mammary gland tumours?
- typically small, purebred dogs –> Chihuahua, Maltese, Dachshund
- but larger ones can have them, too –> English Springer Spaniels (BRCA mutations!), GSH, Dobbies, Pinchers
How does diet/ obesity play a role in mammary gland tumours?
- Being underweight during puberty has a significant protective benefits against MGT
- eating red meat / obese can increase risk
What are some possible mechanisms in which estrogen contribute to tumorigenesis?
- it can increase mutation and aneuploidy
What are some possible mechanisms in which progesterone contribute to tumorigenesis?
- it induces growth factors/ growth factor receptors, and Insulin-like growth factors (IGF-1)
- IGF-1 has both proliferative and survival factors for breast tissues
How does the hormonal receptor status correlate with the aggressiveness of the tumour?
Inverse relationship:
- more hormone receptors = more well differentiated/ less aggressive
What’s the likelihood of having 1+ mammary gland tumours on presentation?
70%
What’s the diagnostic utility of FNA for mammary gland tumours?
- correlation with cytology and histopathology = 68-93%
- sensitivity / specificity for malignant MGT = 88% & 96%
What’s the staging system for canine epithelial mammary gland tumours?
What’s the difference between “simple” and “complex” mammary tumours?
Simple = composed of only 1 cell type, resembling either luminal epithelial cells or myoepithelial cells
Complex = composed of both cell types, and the myoepithelial cells extend into the interstitium
What are the most common mesenchymal tumours of the mammary gland in the dog?
1 = OSA
- chondrosarcoma, fibrosarcoma, hemangiosarcoma
What’s the grading system for cat and dog mammary carcinoma?
Total score:
- 3-5 = Grade I, well differentiated
- 6-7 = Grade 2, moderately differentiated
- 8-9 = Grade 3, poorly differentiated
What’s the grading system for invasive mammary carcinoma in cats?
How does the different histotypes of carcinoma influence survival?
- Adenosquamous CA= MST 18m
- Comedocarcinoma = 14m
- Solid carcinoma = 8m
- Anaplastic = 3m
What are the 3 clinical prognostic factors for canine mammary gland tumours?
- Tumour size (>3cm)
- LN status
- WHO stage
What’s the complication rate of chain mastectomy in dogs?
77%!
If new mammary tumours tend to develop on the ispilateral chain, why is chain mastectomy not gold standard for dogs?
in the same study, 42% of dogs did not develop more MGT, so a radical chain mastectomy would have been unnecessary
What’s the ideal surgical dose for canine mammary gland tumours?
- depends on the tumour size/ characteristics/ whole clinical picture
- lumpectomy with sufficient margins may be sufficient for solitary, small, freely movable mass
- fixed but small masses may still be ok with local mastectomy
- but if large/ multiple, will need a larger surgical dose
OHE should always be performed prior to mass removal
What’s the difference in survival in dogs between complete and incompletely removed mammary gland tumours?
Complete: MST: 22.8-30 months
Incomplete: MST 2.5-15.5 months
What chemotherapy is typically used for canine mammary gland tumours?
anthracycline (doxorubicin)
small report of benefits with desmopressin
What are the 3 main risk factors for feline mammary gland tumours?
- age
- breed (Siamese)
- hormonal influence
What’s the % of mammary gland tumour risk reduction based on age of OHE in cats?
OHe performed:
- at < 6m old: 91% risk reduction
- 7-12m: 86% reduction
- 13-24m: 11% reduction
No benefit after 24m…
What’s the connection with progestin treatment and mammary gland tumour development in cats?
- unlike the dogs, the progestin treated cats don’t tend to develop mammary gland tumours earlier
- male cats treated with progestin can develop malignant mammary tumours (progestin use was noted in 36% of male cats presented with MGT)
What’s the likelihood of finding multiple mammary gland tumours in the cat?
60%
How is feline mammary tumours staged?
How does tumour grade effect of MST on feline mammary carcinoma?
Modified vs Elston & Ellis:
- Grade 1: MST 31m vs 36m
- Grade 2: 14 vs 18m
- Grade 3: 8 vs 6m
What’s the major difference between the original Elston & Ellis grading system an the modified grading system for feline MGT?
The modified one includes lymphovascular invasion
What are some clinical prognostic factors for cats mammary tumours?
- tumour size
- LN status
- Breed (DSH better? Siamese worse?)
- Age (?) –> a prospective study didn’t find a difference between >10 and < 10 yo
Which is the most consistent prognostic indicator for feline mammary gland tumours and how does it influence MST?
Size!
- <2cm (<8cm3): with radical mastectomy, MST >3y
- 2-3cm (8-27cm3): MST ~ 2y
- >3cm (>27cm3): MST ~6m
How does LN status effect survival of feline mammary gland tumours?
Those with positive LN died within 9months.
Another study found that though LN status is associated with shorter PFST and increased risk of death, about 1/3 did not have any further metastasis
What’s the recommended surgical dose for cats with mammary gland carcinoma?
bilateral (staged) mastectomy
What are the outcome difference in surgical dose for feline mammary gland carcinoma?
- bilateral chain mastectomy can significant improve DFI and ST
- median PFS 542 days (1.5y; bilateral) vs 289 days (0.8y; unilateral)
What’s the benefit of adjuvant chemotherapy for feline mammary gland tumours?
- unilateral mastectomy + doxorubicin-based chemo: MST = 1998 days (~5.5y)
- Sx only: MST = 414 days
- 50% of cats developed local recurrence (further supports bilateral mastectomies)
- another study found significant improvement in disease-specific survival for those with adjuvant chemotherapy post-op
What’s the likelihood of finding a metastatic LN with lymphadenectomy during feline malignant mammary tumours?
48/51 (94%); 41/93 (44%); 17/66 (26%)
How is fibroepithelial hyperplasia treated?
OHE or medical hormonal therapy
What’s the response rate of chemotherapy to macroscopic feline mammary carcinoma?
ORR: 40-50% to doxorubicin/ cyclophosphamide
What’s the response of canine stage II-IV mammary carcinoma treated with neoadjuvant doxorubicin/cyclophosphamide comb vs. paclitaxel?
- Doxo/Cyclo: PR 66.6%; CR in 33.33% of triple (-)
Paclitaxel: PR 86.66%; CR in 14.29% of the luminal A subtype
What’s the outcome of cats with stage IV mammary carcinoma with or without adjuvant therapy?
- overall mean TTP = 23 days
- mean overall tumour-specific survival = 44 days
- Symptomatic TPP = 14 days vs 128 days (significant difference)
- There was no significant difference in median TSS between MTD, metronomic, or Palladia, but toxicity was noted in 2/3 of MTD, 20% of MC, and 30% of Palladia.
What’s the impact of histological subtype on survival of canine mammary carcinoma?
- carcinosarcoma, adenosquamous carcinoma, and anaplastic carcinoma subtypes were associated with the poorest prognosis
- age, histological grade, and lymphatic invasion status significantly correlated with tumor-specific survival.
What’s the utility of beta-catenin, TAZ/YAP expression in human, dog, and cat mammary gland tumours?
active β-catenin protein expression was higher in tumors than in healthy tissues for all three species, and YAP/TAZ expression was notably higher in triple negative breast cancers compared to HBC ER(+) and in feline mammary tumors compared to canine mammary tumors.
What’s the outcome of a prospective study on the pre-op use of desmopressin for canine mammary carcinoma?
no significant difference in time to primary metastasis or survival between the two groups
- the result is different than the previous studies
- power? lack of OHE in the previous studies?
What’s the prognostic significance of IHC and histology on canine mammary carcinoma?
- stage 1 complex carcinomas = lowest incidence of metastases,
- triple-negative tumors were mostly in advanced stages and associated with vascular invasion.
- Estimated survival time was shorter triple-negative tumours and those with high COX-2 expression.
- Anaplastic/ inflammatory carcinomas had the worst prognosis with a high proportion of triple-negative tumours in this category
What’s the complication rate and factors that influence the complications rate for dogs undergoing mastectomy?
- overall complication = 16.9% (26/154)
- 34.6% of these cases requiring hospitalization.
- high body weight, undergoing bilateral mastectomy and post-op antibiotic administration –> significantly increased odds of complications,
- concurrent OHE or OE decreased these odds.
How does expression of HIF-1alpha and VEGF influence outcome of feline mammary carcinoma?
- HIF-1α and VEGF were overexpressed in 69.4% and 77.8%. respectively,
- HIF-1α overexpression significantly correlated with the overall survival rate
- neither correlated with histological grade or metastasis.
Are multiple mammary tumours on presentation indicative of malignancy?
one study found 85% were benign, 15% were malignant.
- dogs with multiple mammary masses were not significantly more likely to have malignancies compared to those with single masses
- Age and reproductive status were also not significantly associated with malignancy.
What’s the outcome of feline mammary adenocarcinoma treated with Palladia?
17 cats total.
- median PFS = 91d
- MST = 145d
Clinical benefit was seen in 12 (64.7%) cats and an objective response was seen in six (35.2%) cats.
- 5% CR (1)
- 29% PR (5)
- 35% SD (6)
- 29% PD (5)
What’s the outcome of adjuvant doxorubicin vs metronomic cyclophosphamide and meloxicam vs surgery alone for cats with mammary carcinomas?
Adjuvant chemo didn’t make a significant difference!
- group 1 (n = 80) cats treated with surgery,
- group 2 (n = 34) Sx + doxorubicin
- group 3 (n = 23) cats Sx + low dose metronomic cyclophosphamide and meloxicam
- The median DFI was 270, 226 and 372 days in groups 1, 2 and 3, respectively.
- The median OS was 338 (group 1), 421 (group 2) and 430 (group 3) day
