Cancer Genetics - Hereditary Breast+Gyn

studied byStudied by 0 people
0.0(0)
learn
LearnA personalized and smart learning plan
exam
Practice TestTake a test on your terms and definitions
spaced repetition
Spaced RepetitionScientifically backed study method
heart puzzle
Matching GameHow quick can you match all your cards?
flashcards
FlashcardsStudy terms and definitions

1 / 63

encourage image

There's no tags or description

Looks like no one added any tags here yet for you.

64 Terms

1

Breast Anatomy

  • 15-20 Lobes per breast

  • 20-40 Lobules per lobe

  • 6-8 Ducts drain lobes to the nipple

    • Most breast cancers occur in the ducts

  • Nerves throughout the breast

  • Lymph Nodes and Blood Vessels: help fight infection

New cards
2

Gynecological System

  • Vagina: external to Uterus

  • Cervix: Opening and bottom portion of uterus

  • Uterus: Endometrial lining

    • Polyps

    • Fibroid

  • Fallopian Tubes

  • Ovary

    • Cysts

New cards
3

Non-Modifiable Risk Factors for Breast Cancer

  • Being female (prevalence 1/8 vs 1/700 men)

  • Aging

  • Ethnicity

    • Black women 4% lower incidence than white women, but 40% higher death rate

  • Certain breast conditions : (LCIS, atypical hyperplasia)

  • Hormone exposure: age at mensche/menopause, breast feeding

  • Fam Hx of cancer

  • Inherited gene mutations

New cards
4

Modifiable Risk Factors for Breast Cancer

  • Obesity

  • Alcohol use

  • Physical inactivity

  • Ionizing radiation exposure

New cards
5

Breast Finding: Not Cancer w/ Negligible Increased Cancer Risk

  • Cyst

  • Fibroadenoma

  • Hyperplasia

  • Papilloma

  • Calcifications

  • Radical Scar

  • Benign Phyllodes tumor

New cards
6

Breast Findings Not Cancer w Increased cancer risk

  • Lobular Carcinoma in situ (LCIS)

  • Atypical ductal hyperplasia (ADH)

  • Atypcial lobular hyperplasia (ALH)

  • Flat epithelia (FEA)

New cards
7

Breast Finding Cancer

  • Ducal carcinoma in situ

  • Invasive carcinoma

    • Ductal

    • Lobular

    • Tubular

    • Muscions (Colloid)

    • Medullary

    • Paget’s Disease

  • Malignant Phyllodes tumor

  • Inflammatory breast cancer

New cards
8

Breast Cancer Treatment- Chemotherapy

Anticancer drug used after radiation and surgery

New cards
9

Breast Cancer Treament Radtiaiton

  • straightforward: ionzing radtion to breast cancer tissue

New cards
10

Breast Cancer Therapy - Hormonal Therapy

  • Tamoxifen: targets estrogen and/or progesterone receptor positive cancers

  • Aromatase inhibitors: used in the tretment of breast cancer in postmenopausal women and men by stopping an enzyme in fat tissue (aromastase) from converting hormones into estrogren

New cards
11

Breast Cancer Therapy - Immunotherapy

  • uses body’s own immune system to help fight cancer

New cards
12

Breast Cancer therapy - PARP Inhibitors

  • Effective in BRCA1/2 mutation Cancers (Breast, Ovarian, prostate and Pancreatic)

  • These BRCA1/2 cancer rely heavily on PARP to fix single strand DNA breaks suppressing PARP leads to furthe double strand breaks that BRCA1/2 would normally repair

  • Lack of BRCA1/2 means double breaks cnnaot be repaired, leading to irrevserible DNA breakdown and cel ldeath

New cards
13

Breast Cancer - Surgical Options

  • Lumpectomy

  • Masectromy / Bilateral Masetcomy

New cards
14

Lumpectomy

removal to trumo from breast plus neoadjuvant radtion

<p>removal to trumo from breast plus neoadjuvant radtion</p><p></p>
New cards
15

Masectomry

  • Removal of entire breast tissue and often involves nipple and areola

  • may include SLNB and ALND

<ul><li><p>Removal of entire breast tissue and often involves nipple and areola</p></li><li><p>may include SLNB and ALND</p></li></ul><p></p>
New cards
16

Non-Modifiable Risk Factors for Gynecological Cancer

  • Again

  • Being female

  • chronic conditions (endometriosis, PCOS, diabetes)

  • Hormonal factors (early menarche, late menopause, nulliparity)

  • Infertility

  • Hereditary

New cards
17

Modifiable Risk Factors for Gynecological Cancer

  • Medications (excess estrogen exposure without adequate opposition by a progestin, tamoxifen)

  • Obesity

  • Smoking

New cards
18

Gynecological Tumors

knowt flashcard image
New cards
19

Screening Tests for Endometrial/Ovarian Cancers

  • Pelvic exam

  • Ultrasound/Sonogram

  • MRI

  • Tumor marker 9blood test)

  • Biopsy (usually follow finding by imaging or blood test)

New cards
20

Ovarian/Endometrial Surgical Treatment

  • Hysterectomy (TAH/TH)

  • Bilateral salpingo-oophorectom (BS)

  • LymphNodeBiopsy

  • OMental Biopsy

  • Pelvic Washing

  • Debulking cytoreduction: get all visible cancer out

New cards
21

Ovarian/Endometrial Cancer Radiation therapy

  • Only for Endometrial Cancer NOT Ovarian Cancer

New cards
22

Ovarian/Endometrial Cancer Hormonal Therapy

  • Alternative to hysterectomy to preserve fertility

  • Ex Progesterone

    • Synthetic forms of the naturally-occuring hormone porgesterone; Presnet ina llforms of hormonal birth control

    • Preveny pregnay by inhibiting ovulation

    • Unopposed Estrogen can cause an overgrowth of the endometrium, which may lead to endometrial canca becoming cancersours

New cards
23

Hereditary Breas-Ovarian Cancer Syndrome (HBOC)

<p></p>
New cards
24

HBOC General Testing Criteria - Clinically indicated

knowt flashcard image
New cards
25

HBCO General Testing Criteria - Testing may be concidered

knowt flashcard image
New cards
26

Breast Cancer Susceptibility Genes Testing Criteria

  • Less than 50yo at diagnosis

  • To aid in Systemic treatment decision: PARP (BRAC1/2), Olaparib (HER-2Negative)

  • Pathology/Histology:

    • Triple negative Breast Cancer (Estrogen, Progesterone, HER-2 receptors)

    • Lobular Breast Cancer w history of DIFFUSE GASTRIC CANCER

    • Multiple Primaries

  • Male Breast Cancer

  • Ashkenazi Jewish Ancestry

  • Family history

    • 1 close blood relative with: <50yo Breast, male Breast, Ovarian, Pancreatic, Metastatic Prostate

    • 3 Diagnosises of Breast and/or on same side of the family

<ul><li><p>Less than 50yo at diagnosis</p></li><li><p>To aid in Systemic treatment decision: PARP (BRAC1/2), Olaparib (HER-2Negative)</p></li><li><p>Pathology/Histology:</p><ul><li><p>Triple negative Breast Cancer (Estrogen, Progesterone, HER-2 receptors)</p></li><li><p>Lobular Breast Cancer w history of DIFFUSE GASTRIC CANCER</p></li><li><p>Multiple Primaries</p></li></ul></li><li><p>Male Breast Cancer</p></li><li><p>Ashkenazi Jewish Ancestry</p></li><li><p>Family history</p><ul><li><p>1 close blood relative with: &lt;50yo Breast, male Breast, Ovarian, Pancreatic, Metastatic Prostate</p></li><li><p>3 Diagnosises of Breast and/or   on same side of the family</p></li></ul></li></ul><p></p>
New cards
27

HBOC Guide Lines: Risks and Management

knowt flashcard image
New cards
28

BRCA1 Cancer Risks

  • Breast:

    • Primary: 60-72%

    • Contralateral: 30-40%

    • Male: 0.2-1.2%

  • Epithelial Ovarian: 39-58%

  • Prostate: 7-26%

  • Pancreatic: <5%

New cards
29

BRCA2 Cancer Risks

  • Breast:

    • Primary: 55-69%

    • Contralateral: 25%

    • Male: 1.8-7.1%

  • Epithelial Ovarian: 13-29%

  • Prostate: 19-61%

  • Pancreatic: 5-10%

  • Melanoma: unknown

New cards
30

General Population Cancer Risks

  • Breast 12-13%

  • Ovarian 1-2%

  • Prostate 12-13%

  • Pancreatic 1-2%

    ALWAYS compare to general population RISK!

New cards
31
New cards
32

Risk REduction for HBOC - Breast

  • Hormonal Therapy: 50% reduction

  • Masectomry: 90% reduction

  • Bilateral Salpingo-Oophorectomy (removal of both sides fallopian tube and ovary): 50% reducation (in pre-menopausal women)

New cards
33

Risk Reduction for HBOC - Ovarian Cancer

  • Bilateral Salpingo-Oophorectomy (BSO): 96% reduction

  • Oral Contraceptive Pills (OCPs): 50% reduction (if taken for ~10years)

New cards
34

BRCA Positive Clinical Management - Breast Cancer

Women

  • At 25yo: Clinical Breast Exam 6-12 Months

  • 25-29yo: MRI imaging

  • 30-75yo: Annual mammogram and MRI

  • >75yo: management considered on an individual basis

Men

  • At 35yo: Self Exam + Annual Clincial Exam

  • 50yo: consider mamogram

<p>Women</p><ul><li><p>At 25yo: Clinical Breast Exam 6-12 Months </p></li><li><p>25-29yo: MRI imaging</p></li><li><p>30-75yo: Annual mammogram and MRI</p></li><li><p>&gt;75yo: management considered on an individual basis</p></li></ul><p>Men</p><ul><li><p>At 35yo: Self Exam + Annual Clincial Exam</p></li><li><p>50yo: consider mamogram</p></li></ul><p></p>
New cards
35

BRCA Positive Clinical Management - Ovarian/Fallopian/Perioneal/Uterine

Surgical risk reduction of Ovarian/Fallopian Cancer

  • BRCA1: Recommend Risk-Reducing Salpingo-Oophorectomy (RRSO) at 35-40yo

  • BRCA2: Recommend Risk-Reducing Salpingo-Oophorectomy (RRSO) at 40-45yo {Why? BRCA2 Ovarian cancer present 8-10 years later than BRCA1}

<p>Surgical risk reduction of Ovarian/Fallopian Cancer</p><ul><li><p>BRCA1: Recommend Risk-Reducing Salpingo-Oophorectomy (RRSO) at 35-40yo</p></li><li><p>BRCA2: Recommend Risk-Reducing Salpingo-Oophorectomy (RRSO) at 40-45yo <em>{Why? BRCA2 Ovarian cancer present 8-10 years later than BRCA1}</em></p></li></ul><p></p>
New cards
36

BRCA Psotive Clinical Managment - Prostate

  • Screening/Surveillance: at 40yo

    • BRCA1: consider prostate screening

    • BRCA2: recommend prostate screening

New cards
37

BRCA Positive Clinical Management - Pancreatic Cancer

  • only with Pos. BRCA AND with a Fam Hx of Pancreatic Ca

    • start at 50yo or 10years younger than relative’s diagnosis

    • Endoscopic Ultrasound ( )

    • Magnetic Resonance Cholangiopancreatography (a technique for viewing the bile ducts and pancreatic duct, pancreas gallbladder and liver)

New cards
38

PARP Inhibitor

  • Targets the Poly (ADP-Riobse) Polymerase enzyems: repair single strand breaks via base excsion repair

  • BRCA1/2 cancers have no Double Stranded Break repair system

<ul><li><p>Targets the Poly (ADP-Riobse) Polymerase enzyems: repair single strand breaks via base excsion repair</p></li><li><p>BRCA1/2 cancers have no Double Stranded Break repair system  </p></li></ul><p></p>
New cards
39

Founder Mutations in BRCA1/2

knowt flashcard image
New cards
40

PTEN Hamartoma Tumor Syndrome (PHTS)

  • PHTS syndrome includes the following phenotypes:

    • Cowden Syndrome

    • Bannayan-Riley-Ruvalcaba

    • Adult L’hermite-Duclos disease

    • Protus-like syndrome

    • Autism spectrum disorder with Macrocephaly

<ul><li><p>PHTS syndrome includes the following phenotypes:</p><ul><li><p><strong>Cowden Syndrome</strong></p></li><li><p>Bannayan-Riley-Ruvalcaba</p></li><li><p>Adult L’hermite-Duclos disease</p></li><li><p>Protus-like syndrome</p></li><li><p>Autism spectrum disorder with Macrocephaly</p></li></ul></li></ul><p></p>
New cards
41

Diagnosing Cowden Syndrome

Major

  • Breast Cancer

  • Epithelial thyroid cancer (NON-MEDULLARY)

  • **** Macrocephaly *****

  • Endometrial carcinoma

    Minor

  • other thyroid lesions

  • Intellectual disability

  • Hamartomas intestinal polyps

  • Lipomas

  • Fibromas

  • Genitourinary tumors

  • Uterine fibers

<p>Major</p><ul><li><p>Breast Cancer</p></li><li><p>Epithelial thyroid cancer (NON-MEDULLARY)</p></li><li><p>**** Macrocephaly *****</p></li><li><p>Endometrial carcinoma</p><p>Minor</p></li><li><p>other thyroid lesions</p></li><li><p>Intellectual disability</p></li><li><p>Hamartomas intestinal polyps</p></li><li><p>Lipomas</p></li><li><p>Fibromas</p></li><li><p>Genitourinary tumors</p></li><li><p>Uterine fibers</p><p></p></li></ul><p></p>
New cards
42

Bannayan-Riley-Ruvalcaba Syndrome (BRRS)

PTEN Hamartoma Variant

  • Macrocephaly

  • Intestinal hamartomous polyposis

  • Lipomas

  • Pigmented macules of the glans penis

New cards
43

Proteus Syndrome

  • CAN BE a PTEN Hamartoma Variant

  • Highly variable disorder—> clinical diagnosis hard, molecular diagnosis preferred

  • Hamartoma growth of multiple tissues

    • connective tissue nevi

    • epidermal nevi

    • hyperostoses

New cards
44

Testing Criteria for PTEN

  • Not meeting clinical criteria for CS/PHTS but with:

    • Autism AND Macrocephaly

    • Two or more Trichilemmomas

<ul><li><p>Not meeting clinical criteria for CS/PHTS but with:</p><ul><li><p>Autism AND Macrocephaly</p></li><li><p>Two or more <strong>Trichilemmomas</strong></p></li></ul></li></ul><p></p>
New cards
45

PTEN Hamartoma Tumor Syndrome Cancer Risks

  • Breast: 85%

  • Thyroid (NEVER MEDULLARY): 35%

  • Renal Cell: 34%

  • Endometrial: 28%

New cards
46

CS/PHTS (PTEN) Clinical Managment

  • Thyroid: US starting at 7yo

  • Breast: Screening at 25yo

  • Colorectal: Screening at 35yo

New cards
47

Li-Fraumeni Syndrome (LFS)

knowt flashcard image
New cards
48

Li-Fraumeni Diagnosis/Testing Criteria

  • TP53 positive

    or

  • Three classic clinical positive

New cards
49

Li Fraumeni Chompret

LFS should be suspected in individuals who meet the chompret criteria

  • Has LFS tumor (breast, sarcoma, osteosarcoma, CNS tumor, adrenocortical tumor) AND realtive with LFS tumor before 56yo

  • Multiple tumors, two of which are LFS tumor before 46yo

  • Adrenocortical carcinoma, choroid plexus tumor, or rhabdomyosarcoma

  • Breast cancer before 31yo

New cards
50

Therapeutic Considerations for Lif Fraumeni

  • Radiation therapy should be minimized: potential for downstream malignancies

New cards
51

Li-Fraumeni Screening/Surveillance

  • Breast: 20yo every 6-12 months (Clinical+MRI)

  • Other Cancers: 25yo endoscopy, 18yo Skin exam

  • Pediatric

    • Annual Brain+Body MRI starting in infancy

    • Ultrasound every 3-4 months in infancy

New cards
52

Li-Fraumeni Testing Consideration

  • somatic TP53 detection can confound germline testing: can be detected in blood or slavia —> increase with age, NGS suspetiable

  • Must test tissue other than blood and salvia

  • Comepltle blood count nad perhihpal blood smear must also be done in TP53 postive detection

New cards
53

Hereditary Diffuse Gastric Cancer

knowt flashcard image
New cards
54

Breast Cancer Genes

  • BRCA1 +2, CDH1, PALB2, PTEN, STK11, TP53

New cards
55

CLassic vs ChomperatCriteria for Diagonis of Li Fraumni

knowt flashcard image
New cards
56

Skin Fibroblasts

  • the best option for germline testing tissue for TP53 mutations (Li Fraumeni)

  • Li Fraumni has alot of potenaitl for somatic mutation, blood samples can confound germline many times so skin fibroblasts are the best option

New cards
57

Hereditary Diffuse Gastric Cancer

knowt flashcard image
New cards
58

Signet Ring Cells

  • Associated with Diffuse Gastric Cancer syndrome: presence pathologically confirms diagnosis of DGCS

New cards
59

Controversy on Gastric Cancer Risk reduction surgery

  • Gastrectomy reduces risk <1%

  • But: Quality of life dramatically affected —> major dissatisfaction

New cards
60

Adult vs Child Hereditary Cancer syndromes

  • Adult syndromes: MonoAllelic mutatations

  • Childhood Syndromes: BiAllelic mutations

New cards
61

Francoi Anmeia

  • Bi allalic mutations in BRCA1, BRCA2, BRIP1, PALB2, RAD51C

New cards
62

Ataxia-Telangiectasis

  • Bi allelic pathogenic mutations in ATM gene

New cards
63

Bloom Syndrome

  • Bi allelic pathogenic mutations in BLM

New cards
64
New cards

Explore top notes

note Note
studied byStudied by 18 people
899 days ago
5.0(1)
note Note
studied byStudied by 32 people
794 days ago
5.0(1)
note Note
studied byStudied by 1 person
28 days ago
5.0(1)
note Note
studied byStudied by 103 people
856 days ago
5.0(1)
note Note
studied byStudied by 3 people
761 days ago
5.0(1)
note Note
studied byStudied by 10 people
693 days ago
4.5(2)
note Note
studied byStudied by 39 people
953 days ago
5.0(1)
note Note
studied byStudied by 11 people
776 days ago
5.0(1)

Explore top flashcards

flashcards Flashcard (33)
studied byStudied by 3 people
792 days ago
5.0(1)
flashcards Flashcard (62)
studied byStudied by 5 people
765 days ago
5.0(1)
flashcards Flashcard (82)
studied byStudied by 10 people
56 days ago
5.0(1)
flashcards Flashcard (40)
studied byStudied by 5 people
171 days ago
5.0(1)
flashcards Flashcard (20)
studied byStudied by 115 people
507 days ago
5.0(1)
flashcards Flashcard (25)
studied byStudied by 12 people
468 days ago
5.0(1)
flashcards Flashcard (25)
studied byStudied by 2 people
661 days ago
5.0(1)
flashcards Flashcard (38)
studied byStudied by 38 people
8 days ago
5.0(1)
robot