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Mammary tumors Flashcards

1
Q

What are the 3 major risk factors for mammary carcinoma?

A

age, breed, hormonal exposure

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2
Q

Spayed prior to 1st estrus ___% risk; 2nd estrus __%; 3rd estrus __%

A

0.5, 8, 26

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3
Q

No protective effect of spay after ___ years old

A

4

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4
Q

Recent study found that OHE with benign tumor removal decreases the risk of developing additional tumors (these were in older dogs, confirming that hormonal deprivation even late in life ê risk of tumor development)

Randomized controlled trial 42 dogs with benign tumors – OHE reduced risk by 50%

“New mammary tumor(s) developed in 27 of 42 (64%) intact dogs and 15 of 42 (36%) ovariohysterectomized dogs”

A
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5
Q

Hormonal therapy ____ risk

Treatment with progestins to prevent estrus increases risk by ___x

Progestin-only treatment tends to produce ___ tumors

Estrogen-progestin combinations increase risk for ____ tumors

A

increases

2.3

benign

malignant

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6
Q

Peak incidence at age ___

Tumors in dogs ___ rarely malignant

Risk of malignancy increases with __

Mean age: benign ___ yrs; malignant ____ yrs

A

10

<5

age

7-9, 9-11

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7
Q

List 6 small breeds predisposed to mammary carcinoma?

A

poodles, chihuahua, dachshund, maltese, Yorkie, cocker spaniel

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8
Q

Large breeds predisposed to mammary carcinoma

A

English springer spaniels, Brittany spaniel, English setter, German shepherd, pointers, Dobie, boxier

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9
Q

Evidence for a a genetic risk:

Breed risk is regional (increased risk for boxers in Europe, decreased in USA)

Risk is associated with genetic lineage (some beagle lines have increased risk while others are decreased)

Human germline mutations in BRCA1 or BRCA2 confer an 85% cumulative lifetime risk

A
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10
Q

Minor factor associated with mammary carcinoma?

During puberty (9-12 months) being overweight increases risk (true in humans too)

Being underweight during the same time period is protective

Associated with decreased sex-hormone binding globulins à increased free estrogen, and increased aromatase enzyme which produces estrogens from androgens

Cancer-protective effect of being under-weight is most significant in the first year of life

A

Obesity

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11
Q

Role of estrogen and progestins in cancer:

  • Estrogen and progesterone increase epithelial cell proliferation
  • Estrogen is directly genotoxic, inducing mutations and induction of aneuploidy independent of estrogen receptor
  • Progesterone is tumorigenic via increased production of GH and expression of GH receptors
  • GH — IGF1 — proliferation and survival of mammary epithelium
  • Documented in human breast cancer carcinogenesis

Malignant tumors have significantly higher tissue concentrations of GH, IGF-1, progesterone, and 17B-estradiol than benign tumors

A
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12
Q

Field effect: entire mammary tissue exposed to hormones à most dogs develop tumors in multiple glands

Benign and malignant tumors are on a spectrum:

benign tumor à carcinoma in situ à carcinoma

Areas of carcinoma in-situ present in benign tumors (suggesting zones of transition)

Dogs with benign tumors are at increased risk for having malignant tumors

Dogs with malignant tumors often have concurrent benign ones

A
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13
Q

_____ plays an important role in mammary gland tumor development

A

Hormone exposure

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14
Q

____ tumors more likely than _____ tumors to retain hormone receptors (HRs)

A

benign, malignant

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15
Q

Dogs that are younger, intact, and in estrus more likely to have tumors with ____ expression (“receptor-positive”)

A

HR

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16
Q

Larger, anaplastic, poorly differentiated tumors less likely to be ____ (hormone independence à aggressiveness)

A

receptor-positive

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17
Q

Threshold of expression of ER or PR to determine “receptor positivity” defined as an Allred score >3.79

A
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18
Q

ER

• ____ correlated with malignancy

ER+ breast cancers susceptible to ER receptor antagonists or aromatase inhibitors

____ER receptor antagonist used in humans?

• Side effects high in canines prevents use; OHE/OVE more effective

A

Lack of expression

Tamoxifen

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19
Q

Her-2/neu (EGFR family)

  • Overexpression in human breast cancer associated with ___ prognosis
  • ____% of cases over-express

Studies in dogs have shown discordant results

A

Poor

20-25%

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20
Q

Target for Her-2/neu

A
  • Herceptin / trastuzumab
  • Humanized monoclonal antibody against ECD of HER2 transmembrane receptor
  • Single agent efficacy is poor, but combined with chemotherapy, efficacy approaches 70%
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21
Q

GH/GHR

A

Progestin effects are mediated through increases in GH and GHR

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22
Q

IGF-1

• GH increases proliferation of mammary cancer via IGF-1 signaling

Significantly higher levels of GH and IGF-1 in malignant tumors

A
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23
Q

Common location for mammary gland tumors?

A

Caudal mammary glands

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24
Q

Most dogs are _____ at presentation

A

clinically healthy

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25
Q

5 features of inflammatory mammary CA?

A

Painful and extensive local disease

Metastatic disease is common

Usually systemically sick

No good treatment options

Very poor prognosis

26
Q

Mammary Carcinomas – See table 28.2 (several, both simple and complex)

Carcinoma in situ commonly diagnosed in humans, rarely in dogs due to less frequent early detection

In addition to mammary carcinoma, can also see SCC, adenosquamous carcinoma, mucinous carconima, lipid-rich carcinoma, spindle cell carcinoma

A
27
Q

Mesenchymal/Carcinoma

  • 4 most common are?
  • How does metastasis occur? Common location?
A

OSA, chondrosarcoma, fibrosarcoma, hemangiosarcoma

Metastasis is hematogenous most often to lungs

28
Q

Carcinosarcoma

  • Malignant mixed mammary tumor
  • Uncommon primary neoplasm
  • Has cells of epithelial and mesenchymal origin, both neoplastic
  • Most often presents as carcinoma and osteosarcoma
  • Epithelial component mets via lymphatics to regional LN, lungs; mesenchymal mets via hematogenous spread to lungs
A
29
Q

Hyperplasia/dysplasia/Neoplasia of the nipple

  • Ductal adenoma and carcinoma are rare and only involve the nipple
  • Nipple enlarged and firm
  • Histopathology mimics ductal gland carcinoma
  • Carcinoma with epidermal infiltration = Paget-like, mimics Paget’s disease in women
A
30
Q

Prognosis is best for adenosquamous (____ mo), comedo-(___ mo), solid (___mo)

Prognosis for anaplastic

A

18 month, 14 month, 8 month

3 month

31
Q

Sarcomas and Carcinosarcomas tend to be aggressive and have poor prognosis

Many dogs have >1 tumor, prognosis is determined based on the MOST AGGRESSIVE tumor (which is often the largest)

A
32
Q

Prognosis

Tumor Size

Stage 1 – ___cm, Stage 2 – ____cm, Stage 3 - ____cm, Stage IV – ___involvement

Tumor prognosis changes gradually with ____

Size of tumor is irrelevant if lymph node involvement

A

Stage 1 – 0-3cm, Stage 2 – 3-5cm, Stage 3 - >5cm, Stage IV – LN involvement

Size

33
Q

Prognosis

Lymphatic involvement?

A

For carcinomas, local lymph node involvement is highly prognostic

Lymphatic micro-metastases (clusters from 0.2-2.0mm) do not predict worse outcome

34
Q

The largest contributor to prognosis with respect to stage is?

A

LN involvement

35
Q

___% of patients with one malignant tumor excised via lumpectomy develop a second tumor (survival impact unknown)

A

70%

36
Q

Dogs commonly (58% in on study of 99 intact dogs undergoing regional mastectomy) develop another tumor on the ipsilateral side (more common when initial tumors are malignant)

A
37
Q

Radical mastectomy is associated with ___% post-operative complication rate

A

77%

38
Q

____ recommended for aggressive tumors

Reduces risk of recurrence by ___% and reduces risk of other ovarian/uterine diseases

A

OHE

50%

39
Q

What is recommended with single tumor?

A

wide excision with sufficient margins to be clean is sufficient (2cm margins and 1 fascial plane is recommended for large tumors)

40
Q

Multiple tumors or LN involvement?

A

chain mastectomy or bilateral chain

41
Q

Complete excision or recut should be pursued if incomplete margins as complete margins have found significant benefit over incomplete (MST 22.8 vs 15.4 mo; or 872 vs 70 days, in 2 separate studies)

A
42
Q

What is not recommended for inflammatory mammary carcinoma?

A

Surgery

43
Q

When is systemic therapy recommended?

List 3 reasons when you would recommend?

A

Recommended if high risk tumor, but actual benefit is questionable

>3cm, carcinoma

LN involvement

44
Q

Hormonal Therapy

  • Surgical OHE/OVE is most direct method
  • ER modulators, aromatase inhibitors, LHRH-agonists are also mechanisms to reduce estrogen effects
  • Tamoxifen has significant side effects in canines and not recommended
  • Progesterone receptor-blocker (aglepristone) showed improved DFI
  • OHE at the time of surgery or within 2 years prior showed a survival benefit
  • A recent study found that for HR+ dogs, a modest improvement was seen for dogs undergoing OHE (not statistical), and a significant improvement for dogs with grade II tumors or high median peri-surgical serum estrogen
A
45
Q

Chemotherapy

  • No clearly established benefit in dogs in several under-powered studies of doxo, gemzar, carbo, docetaxel, and mitox
  • ______ with or without chemo have been shown to prolong survival in grade III mammary ca, and in inflammatory mammary carcinoma
  • Chemotherapy for primary mammary OSA has a benefit based on one retrospective study
  • A prospective randomized trial established significant improvement in dogs with grade II or III tumors treated perioperatively with desmopressin, hypothesized to be mediated through improving hemostasis and preventing cancer cells from accessing the vasculature during surgery
  • See table 28.6 for guidelines for systemic therapy
A

NSAIDs

46
Q

Feline mammary tumor

  • ___ most common tumor in cats after lymphoma and skin tumors
  • Most feline mammary tumors are _____
  • ____expression of ER and PR (consistent with malignancy)
  • ____ % are malignant
  • _____ metastasis more common in cats than dogs at presentation
  • Large tumors can become ulcerated and inflamed
A

3rd

aggressive

Low

85-95%

LN

47
Q

Major risk factors for feline mammary CA?

A

age, breed, hormone exposure

48
Q

Age as risk factor for feline mammary CA?

Typical age for presentation?

A

older cats, starting at 7-9 years and increasing with age

49
Q

What feline breed is affected at younger age?

Risk plateus at what age?

A

Siamese are significantly younger when diagnosed; risk plateaus at age 9

50
Q

Hormone Exposure: Sexually intact cats have ___x higher risk than spayed cats

A

7

51
Q

Feline mammary tumors

Protective effect of spay diminishes precipitously after ___ years

Risk decreases by ___ % if OHE < 6 mo

Risk decreases by ___% if OHE 7-12 mo

Risk decreases by ___% if OHE 13-24 mo

A

2 years

91%

86%

11%

52
Q

___ does not alter risk for feline tumors?

Treatment with____ increases risk (benign>malignant), with increased exposure leading to increased risk of malignancy

Rarely occurs in males, but risk higher for males exposed to progestins

A

Parity

Progestins

53
Q

Risk of developing mammary gland tumors in cats is related to _____ but latency period longer for cats than for dogs

Most feline mammary carcinomas are ___ and ____ negative, consistent with higher rate of malignancy and aggressiveness on cats vs dogs

Normal mammary tissue and dysplastic lesions express both ER and PR and this tends to wane with malignancy

Fibroepithelial hyperplasia is progestin-induced and can be cured by OHE or antiprogestins

A

hormonal exposure

ER, PR

54
Q

Clinical Presentation, Diagnostics, Staging of Mammary Tumors in Cats

Generally mature cats that are intact or late spay

Most cats ____ % have >1 tumor at presentation

Which glands are susceptible?

Local LN’s may or may not be affected

Inflammatory mammary carcinoma is rare and similar in course to dogs

A

60%

All glands susceptible; one study says caudal more common

55
Q

Feline mammary tumor

____% malignant with aggressive behavior, lymphatic invasion and LN metastasis

Mammary carcinomas in cats are associated with high percentage of triple-negative, frequent expression of both basal cytokeratins and vimentin, and have the worst prognosis

A

85-95%

56
Q

Feline mammary tumor

Prognosis for G1?

G2?

G3?

A

Grade relationship to prognosis (two systems): G1 31-36mo; G2 14-18mo; G3 8-6mo

57
Q

List 4 important prognostic factors in cats?

A

Tumor size, LN status, breed, and age

58
Q

Feline Prognostic Factors:

Tumor size:

  • 2cm: MST >3 years with sx alone
  • 2-3cm: MST 2 years
  • >3cm: MST <6 month

Lymph node status: LN metastasis significantly _____ prognosis

Breed

Purebred cats have___ prognosis

____ breed has poorer prognosis

Age (+/-)

Studies bias for older cats having more progressed tumors

Prospective study found no difference according to age based on > or < 10 yrs

A
  • 2cm: MST >3 years with sx alone
  • 2-3cm: MST 2 years
  • >3cm: MST <6 month

decreases

poorer

Siamese

59
Q

Treatment – Feline Mammary Tumors

Recommended surgery? PFS for bilateral vs. unilateral

Adjuvant chemotherapy is recommended as it increases disease-specific survival. MST?

Aggressive LN assessment and removal if involved is recommended

Fibroepithelial hyperplasia: Treat with OHE or hormone management

A

Chain mastectomy or Bilateral chain mastectomy

Bilateral PFS 542 days vs unilateral 289 days

With adjuvant chemo - MST 1998 vs 414 days for cats with unilateral mastectomies

60
Q

Feline mammary tumor

Owing to low HR expression, hormone therapy not likely to be effective

Retrospective studies of cats with macroscopic or metastatic disease showed 40-50% ORR from combo DOX-Cytoxan

Recent studies of adjuvant chemo suggest DOX-based protocols increase survival and disease-specific survival

A

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