Neoplasms and Genetic Counseling Flashcards
Breast Cancer epidemiology
● Leading cause of female cancers
● 281,550 cases in the US in 2021 (43,600 deaths)
● 75% occur in women > 50 yrs; Average woman has a 1 in 9 lifetime risk
● Yes, men get it too (women to men; 150:1)
● Strongly correlated with BReast CAncer genes
Breast Cancer etiology
● Most start from the epithelial cells of the glands of the milk ducts
(more to come in “Types” and “Sub-types”)
Breast Cancer risk factors
● Age over 50
● Familial risk – 1st degree relative
● Gene Mutations – BRCA1 and BRCA2
● Hormone-dependent
○ Early menarche
○ Later first full-term pregnancy
○ Late menopause
○ Use of HRT estrogen plus progesterone (6-7 yrs of use doubles risk)
● Obesity
● Moderate alcohol intake
● Chest radiation before age 30 yrs
Breast Cancer presentation
● Breast mass/nodule (document size and location)
○ More likely to be painless
○ Hard and/or irregular
○ Tethered or fixed to chest wall
● Dimpling
● Skin changes “peau d’orange”
● Nipple discharge or retraction
● Enlargement or shrinkage of the breast
Breast Cancer DDX
● Fibroadenoma
● Cysts
● Fat necrosis
● Abscess
● Lymphoma
Breast Cancer diagnosis
● Diagnostic mammogram (not the same as
screening)
○ Takes longer, varied angles, magnification of
area of concern
● Additional imaging usually for higher risk
○ Targeted breast U/S
○ MRI (High sensitivity, but not specific →
increased biopsies)
● Breast biopsy
Breast Cancer types
● Ductal carcinoma in situ (DCIS)– pre-cancer, starting it the milk ducts
● Invasive (advanced DCIS)
● Inflammatory breast cancer (1-5%)
● Metastatic breast cancer
● Subtypes: Triple negative (10-15%)
Breast Cancer staging
● TNM classification
● Genetic test and DNA
sequencing with
specific gene
expression
Breast Cancer treatment
● Based on staging and gene expression
○ HER2, ER, PgR
● Surgical- lumpectomy, partial or complete mastectomy, etc
● Radiation
● Systemic treatments
○ Endocrine Therapy (selective estrogen-receptor modulators “SERM”)
○ Anti-HER2 – monoclonal antibodies (Herceptin)
○ Chemotherapy
Ovarian Cancer etiology
● Epithelial tissue
● Germ cell tumors
● Sex cord-stromal tumors
Ovarian Cancer risk factors
● Age over 50 (63 yo median age at Dx)
● Early menarche or late menopause
● Familial risk
● Gene Mutations
○ BRCA1 – 39–46% lifetime risk of ovarian cancer
○ BRCA2 – 2–20% risk of ovarian cancer
○ Lynch syndrome – 5-10% lifetime risk of ovarian cancer
● Endometriosis/Pelvic radiation possible contributors
Familial risk for Ovarian cancer
○ 2nd degree relative (3.5% increased risk)
○ 1st degree relative (5% increased risk)
○ Two relatives with ovarian cancer (7% increased risk)
Ovarian Cancer S/S
● Early stage – presents with vague and ill defined symptoms
● Late stage – abdominal pain or bloating, early satiety, and/or urinary urgency or
frequency. Menstrual abnormalities in reproductive age (15%)
○ The majority of women present with late stage disease
Ovarian Cancer diagnosis
● Pelvic exam – Adnexal Mass
● Pelvic U/S – Solid mass (hypoechoic)
● Lab studies
○ CA-125
● CT/MRI extent of the cancer
● Surgical excision
○ Pathology
Ovarian Cancer types
● Epithelial (80-85%)
● Germ cell tumors (5%)
○ Found in 2nd and 3rd decades of life
○ Tumor markers to monitor
● Sex cord-stromal tumors (1.2%)
Ovarian Cancer staging
● TNM classification
● Genetic testing
● Human epididymis protein
4, lactate dehydrogenase,
alpha fetoprotein,
carcinoembryonic antigen
Ovarian Cancer treatment
Based on staging
● Total hysterectomy with a bilateral (unilateral) salpingo-oophorectomy
● Chemotherapy
● Radiation (germ cell)
● Supportive care
USPSTF recommendation grading for screening for ovarian cancer
D - no recommendation for screening
Uterine Cancer: different types of tumors
○ Benign – uterine fibroid (leiomyoma)
■ More common in black females, 2-3x > than in white females
○ Malignant
■ Most (80%) are endometrial adenocarcinomas
■ Lifetime risk of 2.4% for white females, and 1.3% for black females
● Estrogen plays important role in gland proliferation
Uterine Cancer risk factors
● Obesity
● Postmenopausal estrogen treatment
● Lynch Syndrome
● Long-term use of Tamoxifen
● Pelvic radiation
Black box for tamoxifen
Tamoxifen antiestrogenic in the breast but is
associated with weak estrogenic effects in uterine epithelium→ increased risk of endometrial cancer
Uterine Cancer S/S
● Postmenopausal bleeding
● Premenopausal women
○ Atypical bleeding – between cycles, heavy, or prolonged
○ Reproductive dysfunction – infertility, miscarriage, complications
● Pelvic mass…with or without bleeding
● Pelvic pressure/pain (+/-)
Uterine Cancer DDx
● Complications of early pregnancy
● Endometrial hyperplasia (w/ or w/out Atypia)
● Endometrial or cervical polyps
● Intrauterine device
● Various genital or metastatic cancers
● Hormonal/perimenopause
Uterine Cancer Diagnosis
● Imaging – Ultrasound
● Biopsy – endometrial biopsy w/o or w/ Hysteroscopy
Uterine Cancer types
● Endometrial (Endometrium) – 80%
● Sarcoma (Myometrium) – 3-9% (50-60 years old)
○ Leiomyosarcoma (1-2%)
○ Endometrial Sarcoma (8%)
● Leiomyoma (Smooth muscle tumor) – Benign
Uterine Cancer staging
● TNM
○ Stage 1 – 75-85% of disease is localized
to the uterus
○ Stage 2-3 – 10-20%
● Genetic testing – Lynch
Uterine Cancer treatment
○ Hysterectomy with removal of ovaries and fallopian tubes
■ Stage 1
○ Chemotherapy for later stages
■ Node involvement
○ Hormonal
■ Progesterone
○ Immunotherapy
Leiomyoma
● Most common pelvic neoplasm (benign) in reproductive years
● More common in black women
● Increase in incidence 50-60 years old
● When symptomatic – abnormal uterine bleeding and/or pelvic
pain/pressure, reproductive dysfunction
Leiomyoma Exam/Dx
● Abdominal/pelvic exam, Fundal height
● Pelvic U/S – Transvaginal ultrasound has high sensitivity (95 to 100 percent
Leiomyoma US findings
● Well defined, solid, hypoechoic mass
● Calcification is seen as echogenic foci
with shadowing
● Cystic areas of necrosis or
degeneration may be seen
Screening – Endometrial/Uterine Cancer
No recommended screening
Postmenopausal bleeding is cancer until proven otherwise
Pap smears are classified by a naming system called the Bethesda system and include:
● ASC-US: Atypical squamous cells of
undetermined significance
● ASC-H: Atypical squamous cells in which
high-grade lesions cannot be excluded
● LSIL: Low-grade squamous intraepithelial lesion
○ Cellular changes consistent with CIN I
● HSIL: High-grade squamous intraepithelial
lesion
Biopsied lesions of the cervix are classified with Cervical Intraepithelial Neoplasia (CIN) and include:
● CIN I: Disordered grown of the lower third of the
epithelial lining
○ Mild Dysplasia – 60% resolve on their own
● CIN II: Abnormal maturation of the lower 2/3 of the
lining.
○ Moderate Dysplasia
● CIN III: Involves more than 2/3 of the epithelial thickness
○ Severe Dysplasia
● Cancer in Situ (CIS): Involves the full thickness of the
epithelium
A biopsy must be obtained to officially diagnose ______
CIN II or CIN III (cervical cancer)
Which strain of HPV is found in 50-70% of cervical cancers?
HPV-16
Cervical Cancer Risk factors
● Smoking increases risk of cervical
cancer by 2-4x
● Immunosuppression
● HIV infections
● Hx of STIs
● High parity
● Oral contraceptive use
Cervical Cancer S/S
● Usually no signs or symptoms with CIN
● Abnormal vaginal bleeding
● Post-coital bleeding
● Blood stained discharge
● Pelvic pain (often unilateral)
Cervical Cancer PE
● Normal appearing cervix
● Enlarged, irregular, and/or firm cervix
● Friable, bleeding, or cauliflower-like cervix
● Cervical ulceration
● Cervical necrosis
● Loss of cervical mobility
Cervical Cancer diagnosis
● HPV testing
● Schiller test (staining with “Lugol’s solution” or toluidine blue)
● Colposcopy
○ Biopsy
■ Endocervical sampling
■ Conization
Cervical Cancer types
● HPV
● HSIL/CIN II/CIN III
● Squamous Cell
○ Adenocarcinoma in
situ (ACIS)
○ Adenocarcinoma
Cervical Cancer staging
● CT scan / MRI
● Cystoscopy or proctoscopy
Cervical Cancer Treatment
● Expectant management
○ CIN I with cytology of low grade lesion (ASCUS or LSIL)
● Treatment
○ CIN I with cytology of high grade lesion (ASCH, HSIL, or AGC-NOS)
○ CIN II/CIN III
Cryotherapy, laser ablation, conization, superficial or deep excision by the loop electrosurgical excision procedure (LEEP),
deeper excision, hysterectomy, post-op radiation and chemotherapy
Vaginal/Vulvar Cancers S/S
Vaginal
● Most often asymptomatic, found incidentally on routine pelvic exam
● Postmenopausal vaginal bleeding and/or postcoital bleeding
Vulvar
● 50% vulvar pruritus and/or a vulvar mass
● 20% asymptomatic, found incidentally on routine pelvic exam
● Bleeding or vulvar pain
Vaginal/Vulvar Cancers diagnosis
● A complete history and physical/pelvic exam
● Cervical cytologic examination, Endometrial biopsy, Colposcopy
● Biopsy
Vaginal/Vulvar Cancers staging
CT/MRI chest/ab/pelvis
Vaginal/Vulvar Cancers treatment
Vaginal Cancer
● Stage 1 – Surgery (hysterectomy with possible lymph nodes)
● Stage 2+ – Radiation
Vulvar Cancer
● Surgery (with possible lymph node resection)
○ Postoperative radiation and possibly chemotherapy
Cancer Predisposition Syndrome
○ Mutated allele from one parent (not sufficient to initiate
a tumor) and a normal allele from the other parent. If
the normal allele develops the mutation, tumorigenesis
can be initiated
○ Increased risk of cancer, possibly multiple types, at an
earlier age
○ Over 100 hereditary cancers exist
○ Rare
○ Predominantly autosomal dominant
Hereditary cancers are inherited in what pattern?
Predominantly autosomal dominant
Who to Test for hereditary cancers based on personal history?
● Personal Hx of breast, ovarian, pancreatic or
metastatic prostate cancer (especially if under 45
years old)
● Personal Hx of colon or uterine cancer under 50
years old
● Personal Hx of 2 or more cancers
Who to Test for hereditary cancers based on family history?
Ashkenazi Jewish ancestry
● Early breast or colon cancers (<49 years old)
● Any ovarian, pancreatic, metastatic prostate, male breast cancer, endometrial/uterine, rectal, or stomach cancer
● Known hereditary cancer in the family
● 2 Dx of breast or colon cancer in a single first degree relative (any age)
● 3 or more breast cancers in relatives on same side of the family
0 Early breast or colon cancers (<49 years old)
1 Ovarian, pancreatic, metastatic prostate, male breast cancer,
endometrial/uterine, rectal, or stomach cancer
1 Known hereditary cancer in the family
2 Dx of breast or colon cancer in a single first degree relative (any age)
3 or more breast cancers in relatives on same side of the family
Chemoprevention for cervical cancer
HPV vaccine
Chemoprevention for breast cancer
○ Tamoxifen and Raloxifene
● Tamoxifen: Risk must outweigh benefit due to slight higher risk of endometrial cancers
■ Raloxifene – slightly less effective, but had lower incidence of thromboembolic events and endometrial cancer
Who should get Prophylactic Surgery for breast cancer?
● BRCA-1 and BRCA-2
○ High risk of breast and ovarian cancer
○ Prophylactic bilateral mastectomy
○ Prophylactic salpingo-oophorectomy
Tyrer-Cuzick Score
A score/percentage is calculated to identify the patient’s “10 year risk” and “lifetime risk” of breast cancer
This risk score is calculated based on several characteristics.
● Hormonal Hx (age menses, age with first child born, age of menopause, use of HRT
● Height, weight, past history dense breast tissue on mammogram or breast biopsy
● Pt’s family history of breast and ovarian cancer for 2 generations and presence or
absence of BRCA1 or BRCA2 mutations
If lifetime risk is greater than ____%, qualifies for increased screenings, including
breast MRI and mammogram annually (additional provider based exams and
other strategies may be done based on risk)
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