Ch 82 Mammary tumors Flashcards
anatomy
- Dogs have five pairs of mammary glands:
- cats have 4 pairs
- compound tubuloalveolar gland
- Myoepithelial cells line the secretory unit
- blood supply mainly originates from the lateral and internal thoracic arteries and the external pudendal artery
- three cranial glands: lateral thoracic artery and cranial superficial epigastric artery
- two caudal glands: caudal superficial epigastric artery and deep circumflex iliac arteries
lymph nodes
- (glands 1 and 2) axillary lymph center +/- superficial cervical and sternal lymph nodes
- (glands 3 and 4) inguinofemoral +/- axillary lymph center
- (gland 4) +/- medial iliac + popliteal lymph center
- (gland 5) inguinofemoral + medial iliac +/- popliteal lymph center
- Ipsilateral and contralateral anastomoses between glands
cats: G3 may drain to axillary and G2 may drain to inguinal, +/- to sternal
incidence
- most common tumors in intact female dogs
- predisposed, Poodles, Spaniels, Dachshunds, Doberman, GSD
- median age malignant higher (9.5 years) than benign tumors (8.5 years)
- risk for benign 2-5x higher than malignant
- incidence of malignant tumors in female dogs varies greatly (2% to > 20%) > reflect neuter status of population
- incidence increases with increasing age
- development of malignant mammary tumors is hormone dependent
- progestins increase the risk for benign
What hormones and growth factors may predispose to mammary tumour development
- Combination of oestrogen and progestin together (receptors present > 90% of benign tumors, ~50% malignant, indicate that a loss of hormone dependency frequently occurs in malignant tumors)
- Growth factor indirectly via IGF-1 and IGF-2
- Prolactin
most important risk factor?
most important risk factor for malignant mammary tumor development = choice and time of spaying
- Spayed before 1st oestrus - 0.5%
- Before 2nd oestrus - 8%
- Before 2yo - 26%
Spaying at a later age may still reduce the risk for benign tumors but not malignant
effect of ovary removal on tumor development is generally acknowledged,
- systematic review: evidence concerning the effect size and timing is weak and has a moderate to high risk for bias.
What genetic factors may be associated with mammary tumours?
- Overexpression of protooncogene c-erb-2
- p53 tumour suppressor gene mutations
- expression of tumour suppressor genes BRCA1 and BRCA2 and RAD4
- Overexpression of adhesion moledules CD44
- Decreased expression of E-cadherin
- VEGF expression for angiogenesis
- COX2 expression
- Obesity at 1yo or younger
Inflammatory Carcinoma
mastitis carcinomatosa
- rapidly progressive, highly metastatic disease, mostly seen in sexually intact dogs
- massive edema (including limbs); erythema, ulceration, firm consistency, pain, anorexia; and generalized weakness.
- can be primary or secondary.
- may mimic mastitis (perfomr FNA)
highly invasive and high rate of mets, MST 25-60 days
Describe the TNM staging of mammary tumours
Histologic Subtypes
- malignant: complex carcinoma composed of luminal epithelial and myoepithelial cells (relatively common), simple tubulopapillary carcinoma (frequent), solid carcinoma (common), and anaplastic carcinoma (fairly common).
- benign adenoma
Vazquez 2023 – review, immunohistochemical subtypes
- expression of oestrogen (ER) and progesterone (PR) receptors → better px
- ER-, PR+ → poorer outcome vs ER+, PR+; ER-, PR- worst px
- subtypes: luminal A, luminal B, HER-2, triple-negative (ER/PR/HER-2 negative)
- Ki-67 negative px indicator in luminal A and B for metastasis and survival
- E-cadherin – low expression/absence → more aggressive/metastatic
- triple neg and HER-2+
- HER-2 overexpression correlated with malignancy and high grade
- COX-2 overexpression associated with metastasis (increased angiogenesis)
presentation
- single or multiple (>60% of cases)
- audal glands (4 and 5) are most commonly affected
- Benign: usually small, well circumscribed, and firm on palpation
- malignancy: rapid growth, poorly circumscribed or invasive growth, fixation to skin or underlying tissues, and ulceration or inflammation.
Dx and staging
- Malignant tumors often lack cytologic signs of malignancy
- sensitivity of 88% to 96% and a specificity of 96% to 100% have been reported for cytologic diagnosis of canine malignant
- nondiagnostic samples varied from 14% to 28%
- Biopsy? if sx possible, treatment for benign and malignant lesions is essentially the same
- indolent for a longer time may suddenly turn into rapidly growing malignant masses
Staging
- Regional lymph nodes should always be investigated
- chest assessment always
- G3/4 > ultrasond abdomen
- Distant metastasis: lungs, liver, spleen, kidney, and bone, and in distant lymph nodes
- incidence of distant metastasis at initial evaluation 6% to 38%
- metastasis rate to the lymph nodes varies 20-100% (44% to 50% for malignant tumors)
- lymph node depends on histological type and size of tumor
What are the surgical options for mammary tumours?
- Lumpectomy - small under 0.5cm tumours, known to be benign
- Simple mastectomy - Small, centrally located tumours for which mastectomy achieves 2-3cm margins
- Regional mastectomy - En bloc removal of glands 1-3 or 3-5
- Chain mastectomy - multiple nodules, tumours in the 3rd gland, or large masses over 1cm with fixation or otherwise suspicious for malignancy. Unilateral or staged bilateral (4-6weeks)
- Radical mastectomy is recommended in cats regardless of tumour size
sx
choice is surgical resection, except for inflammatory carcinoma or presence of distant metastasis, for which prognosis is poor and surgery usually does not improve outcome.
- Tumors larger than 0.5 to 1.0 cm or showing evidence of invasiveness should be widely excised with 2- to 3-cm margins.
- fixation to the underlying muscle fascia or the skin is suspected, the fascia and first muscle layer and skin should be included
- glands 1 to 3 and glands 4 to 5 are confluent, and single mammectomy may be more complicated
- removal of micrometastatic lymph nodes may be therapeutic in mammary cancer
- lymphatic communication between several glands, metastasis may be unpredictable
- Bilateral mastectomy removes more than 95% of all mammary tissue
58% of dogs developed a new tumor in the remaining ipsilateral glands after regional mastectomy for a single tumor
prognosis
- histologic tumor type
- grade
- invasiveness
- size
- lymph node mets/stage
- carcinomas with well-differentiated nuclei: 24% recurrence or metastasis
- 60% recurrence/mets carcinomas with stromal invasion, 97% with lymph or blood vessel invasion
- malignant median diameter 4.7 cm versus 2.1 cm for benign
- <3 cm (T1) in diameter had significantly better median survival (22 months)
- presence of lymph node metastasis is associated with a poorer prognosis re recurrence and MST> 80% recurrence within 6 months compared with 30%, shorter MST at 2 years
- median survival was 5 months for dogs with distant metastasis
- l.n. with micromets (<2mm) extirpated similar survival as no mets. Macromets (>2mm) still associated with poor MST
- lymphadenectomy may be of therapeutic value
- molecular phenotypes (luminal A, luminal B, basal, and HER-2 overexpressing tumors
What treatment is available is node mets are confirmed for mammary tumours
- mixed results with chemo benefits, overall MST appears longer
- Adjuvant carboplatin chemotherapy
Radiation therapy has not been evaluated
protective effect of estrogen suppression (ovari[ohyster]ectomy), except when performed in young animals (<2 years), has not been observed in dogs with mammary tumors.
What is the effect of spaying on development of mammary tumours in cats?
Reduced by 91% and 86% when spayed by 6m of age and 1yr of age respectively
feline mammary tumor
- > 85% histologically malignant
- hormones seem to play an important role: spayed before 1 year of age had signifacnt reduction in risk for compared with intact cats.
- similar loss of hormone dependency during malignant progression
- HER-2 protooncogene and Ki67 increased expression with malignancy
- VEGF expression was significantly correlated with histologic grade and overall surviva
- Cox-2 xpression was found in 87% to 96% of feline mammary carcinomas
tumor biology
- single or multiple (>50% of the cases)
- ulceration (>25% of the cases),
- invasive growth
- ylmph nodes, lungs, pleura (carcinomatosis), liver, diaphragm, adrenal glands, and kidney
- > 80% of feline mammary tumors are adenocarcinomas.
- common subtypes: tubular, solid, papillary, and cribriform carcinomas (complex uncommon)
Fibroadenomatous Hyperplasia
- hormone-dependent growth disturbance> high levels of endogenous or exogenous progestins induce rapid proliferation of mammary tissue, resulting in massive mammary gland enlargement
- young (< 2 years old),
- sexually intact cats after progestin treatment; puberty; first estrus cycle, pregnancy, or pseudopregnancy.
Tx
- removal of the hormonal influence = Ovari(ohyster)ectomy may lead to gradual regression
- frequently not successful > treated by mammectomy or mastectomy.
- progesterone receptor blocker aglepristone (full remission in 21/22 cats0
surgery
if no distant mets
- Preoperative biopsies are rarely indicated because more than 80% of mammary tumors are malignant.
- treatment of choice is radical mastectomy of the affected side, regardless of tumor size
- underlying fascia and a layer of abdominal muscle if fixed
chemo: trial comparing sx alone with Sx+chemo (doxo, cyclophos) found no significant advantage for use of chemotherapy
prognosis
- histologic grade
- lymph node or lymphatic invasion
- tumor size
- extent of surgery
- Survival for tumors <3cm in diameter was significantly better (1.5-3yr)
- aggressive surgery results in better MST
- percentages of cats that died during the first postoperative year were 0%, 42%, and 100% for histologic grades I, II, and III, respectively
- pulmonary metastasis died within 5 months
Contrast enhanced computed tomography assessment of
superficial inguinal lymph nodemetastasis in caninemammary
gland tumors
Christina Soultani
VUR
At all time points, the median density value in the center and in the periphery was significantly higher in metastatic than in nonmetastatic
SLNs. confirmed with histopath.
The findings from the current study appear to support the initial
hypothesis that metastatic nodes may show higher density enhancement
values inCE-CT than normal ones.
within 3 min from contrast medium administration
Epidemiology and risk factors for mammary tumours in female cats
Price 2023
- increasing risk seen in older cats and with purebred status
- Median survival after the diagnosis of mammary tumour cats was 18.7 months
Metastatic feline mammary cancer: prognostic factors, outcome and comparison of different treatment modalities - a retrospective multicentre study
Gonçalo Petrucci 2021
Stage IV feline mammary tumours, n=73
- overall poor prognosis, some cats survived >6 months, indicating that adjuvant treatment may be an option
- overall: mean time to progression (TTP): 23d, tumour-specific survival (TSS): 44d
- pleural effusion → lower TSS (14d)
- chemotherapy: max tolerated: median TSS 58d, 66.7% toxicity
metronomic: median TSS 75d, 20% toxicity
toceranib: median TSS 63d, 30% toxicity
- overall: TTP 50d, TSS 63
Incidentally diagnosed mammary gland tumors are less likely to be malignant than nonincidental
mammary gland tumors
Murphy 2023
96 female dogs
In dogs with incidental MGTs, 82 of 88 (93%) tumors were benign and 6 of 88 (7%) were malignant. In dogs with nonincidental MGTs, 75 of 107 (70%) tumors were benign and 32 of 107 (30%) were malignant
Most incidentally diagnosed MGTs are benign and allow for a good prognosis after excision. Small dogs and dogs with MGTs < 3 cm in diameter are the least likely to have a malignancy.
Factors influencing complications following mastectomy
procedures in dogs with mammary gland tumors:
140 cases (2009–2015)
Evans 2021
140 female dogs that underwent 154 separate mastectomy procedures, retrospective
complication rate 16.9% (26/154); of these, 9 (34.6%) required hospitalization
Seven of the 9 hospitalized dogs had an infection or abscess
Seromas were the most common
Previously spayed dogs with a large body size that underwent the most extensive (bilateral) mastectomy procedures had increased odds of having postoperative
complications
Prevalence of malignancy in masses
from the mammary gland region of dogs
with single or multiple masses
John Litterine-Kaufman 2019
137 (85%) were classified as benign or nonneoplastic and 24 (15%) as malignant.
(5%) dogs had masses that
were not of mammary gland origin
Dogs with multiple masses in the mammary gland region were not significantly
more likely than dogs with single masses to have a malignancy
Collivignarelli 2021 – lymphatic drainage of mammary tumours can have patient variation
Pimentel 2024 – review of lymph nodes and draining of canine mammary tumours + LN extirpation
vital dyes have good evidence to support use
- contrast imaging → specific tumour drainage but supporting evidence small
Da Silva Soares 2023 – prognostic factors for tumour-specific survival and DFI, n=385 dogs
VMI
carcinoma in mixed tumour most frequent (44%) → best px
- higher stage and previous history → lower CSS
- histologic grade and age best independent parameters for TSS, DFI and overall survival
- multivariate analysis
