Oncology Flashcards
What are concerning features of adnexal masses?
>10cm irregular outline or cyst wall papillary excrescences solid components ascites thick septations
Tumor markers: dysgerminoma
LDH (V HIGH)
bHCG
Tumor markers: immature teratoma
AFP
What are the genes involved in Lynch syndrome?
MLH1 (uterine + ovarian), MSH2 (uterine + ovarian), MSH6 (uterine) , PMS2 (uterine)
What is the genetic inheritance of Lynch syndrome?
Autosomal dominant
What is the risk of Lynch syndrome in women with endometrial cancer?
5-9% if <50 years old
2.3% if >50 years old
What is the risk of uterine carcinoma in patients with EIN on biopsy/D&C?
40% risk of carcinoma on hysterectomy.
Lynch syndrome cancers
ovarian (4-12%), endometrial (25-60%), colon (50-80%), stomach (6-13%). Small % (<5) urinary tract, CNS, HPB, small bowel
40-60% present with endometrial cancer first
STK11 mutation - assocaited cancers, specific gyn risks
Peutz-Jeghers syndrome
hamartomatous polyps of the GI tract and pigmented macules (P = pigemented, J = jejunum)
Associated with increased risk of colon/stomach/small intestine cancer, breast/uterine/sex cord stromal tumor of the ovary, adenoma malignum of the cervix
breast cancer risk 44-50%
ovarian cancer risk 18-21%
risk of adenoma malignum of cervix (rare adenocarcinoma)
PTEN mutation - risks and cancers
Cowden syndrome
Breast (25-50%), hitting age 30-40
Endometrial (5-28%)
Renal, colon, thyroid, and melanoma
TP53 mutation
Li Fraumeni
Associated with sarcomas - osteo/soft tissue, breast cancer, adrena tumors, CR cancer, ovarian
Her2/Neu
Associated with breast ca, ovarian ca, and serous endometrial cancer
What chromosomes are BRCA 1/2 on?
17q and 13q
What is the risk of breast and ovarian cancer in BRCA?
BRCA1 - breast cancer 75%, ovarian cancer 40% (39-46%; earlier onset)
BRCA2 - breast cancer 75%, ovarian cancer appx 20% (10-27%, later onset)
When is RRBSO performed?
BRCA1 - between 35 and 40yo
BRCA2 - between 40 and 45yo
In BRCA, reduces risk of ovarian cancer by 85-90%
Where do you ligate the IP in a RR BSO for BRCA?
2cm proximal to the ovary
Which BRCA has a higher risk of uterine cancer?
BRCA1
Higher risk of serous endometrial cancer
What is the breast screening for BRCA?
Age 25-29; semiannual breast exam, mri annually
Age 30 onwards; semi annual breast exam, breast mri and mammogram alternate q6 months
What are the risk reducing strategies for breast cancer in BRCA carriers?
bilateral mastectomy - 90-95%
RRBSO (if premenopausal) - 40-70% (maybe higher in BRCA2)
tamoxifen - 63% in BRCA2 - esp preventin contralateral breast cancer
Bethesda Guidelines for genetic testing for Lynch Syndrome
- Endometrial or colon cancer <50yo
- Endometrial/ovarian cancer + colon cancer
- Colon cancer w/ specific growth patterns <60yo
- Endometrial or colon cancer and 1st degree relative with HNPHH tumor <50yo
- Endometrial or colon cancer w/ 2+ 1st or 2nd degree relatives with HNPCC tumors regardless of age
Amsterdam Criteria for genetic stesting for lynch syndrome
3-2-1 rule
3 or more relatives with colon, endometrial, intestine, ureter, or renal pelvis cancer
2 or more successive generations affected
1 or more relatives diagnosed before age 50
1 patient is a 1st degree relative of other affected
Surveillance for lynch syndrome pts
Colonoscopy q1-2 years starting age 20-24
Annual pelvic exam
Endometrial biopsy yearly (or q1-2) years beginning age 30-35
TVUS and CA-125 yearly beginning 30-35
Annual UA starting 30-35
Endoscopy q2-3 years starting age 30-35
What factors preclude breast-conserving (lumpectomy) therapy?
- multifocal disease
- large tumor size
- hx radiation to chest wall
- diffuse calcifications
- persistently positive margins
What is the treatment for cervical cancer by stage?
IAI - simple hyst or CKC
IA2-IBI - rad hyst and lymphadenectomy
Locally advanced IIB-IVA - chemotherapy and radiation
Who gets tamoxifen?
Premenopausal women with HR+ breast cancer
5 years of tamoxifen reduces recurrence by 45% and mortality by 32%
Who gets aromatase inhibitors after breast cancer?
Post-menopausal women only (for now)
What’s the biggest risk factor for post-operative sexual dysfunction in vulvar cancer?
Patient age, depression, performance status, and pre-operative sexual dysfunction
What is primary treatment for basal cell carcinoma of the vulva?
Wide local excision
negative margins 4-5mm
Women with endometriosis are at increased risk of what cancer?
Clear cell carcinoma of the ovary
What is the treatment for IBI small cell carcinoma of the cervix?
rad hyst + bl pelvic lymph node dissection
CHEMO next - cisplatin-etoposide
What is the recommended post-surgical surveillance in advanced stage ovarian cancer?
Physical exam and CA-125
No imaging
q3 months for 2 years, q6 months for 3 years, then annually
Gross hematuria after radiation therapy for cervical cancer
Radiation cystitis / hemorrhagic cystitis (5% in 5 years, 7% in 10 years, 9% in 20 years)
mean interval 4 years s/p radiation
tx bladder irrigation, evacuation of clot, embolization and transfusion prn
What is the main risk factor for IP chemotherapy catheter infection?
left colon/colorectal resection at time of placement (contamination)
What does surveillance after endometrial cancer entail?
History and physical. No imaging. No CA-125.
Which patients with vulvar cancer need nodal evaluation?
Depth of invasion >1mm
Which patients with vulvar cancer meet criteria for sentinel nodal mapping
Lesions <4cm
No palpable node / localized disease without obvious node involvement
Squamous histology
What is the preferred screening for women of average breast cancer risk but dense breast?
Digital mammography
In what kinds of cancer patients can you use menopausal hormone therapy?
Hematologic
Colorectal
Cervical
Vaginal/vulvar
What are benefits of transdermal estrogen over oral estrogen?
Decreased risk of blood clots (avoids liver stimulation with first pass effect; oral estrogen risk OR =4)
Decreased elevation in triglycerides (first pass liver)
What hormone therapy can you use in breast cancer survivors?
Vaginal estrogen
DHEA
Ospemifene (SERM)
What are the two vaginal estrogen rings and what is the difference?
Estring - no significant systemic absorption
Femring - does give systemic levels
Ospemifene
Block at Breast
Agonist at Bone
Agonist at vaginal mucosa
dose 60mg/day
What is the dose of estrogen replacement for a young woman <45?
0.1 patch
2mg oral estradiol
What is the chance of having a germline BRCA mutation in a woman diagnosed with high-grade ovarian cancer?
10-24%
What are the BRCA founder groups?
Ashkenazi Jews, French Canadians, Icelanders
What is the usual histology for BRCA- associated ovarian cancer?
serous or endometrioid
What is the risk of ovarian cancer in BRCA1?
39–46% by age 70 years
What is the risk of ovarian cancer in BRCA2?
by age 70 years is 10–27%
What is the risk of finding malignancy in risk-reducing salpingectomy for BRCA?
1-6%
Mostly STIC lesions
What is the risk reduction associated with bilateral tubal ligation?
24% lower risk of ovarian cancer in Nurses Health Study
Swedish risk reduction study - what is the risk reduction of BTL vs salpingectomy?
BTL - 28%
Salpingectomy - 60-65%
Reduced risk compared to women who did not undergo these proceures
Where is the most common location for a STIC lesion?
Fimbriae
How often can opportunistic salpingectomy be performed during vaginal hysterectomy?
75-88% success
What is the risk of uterine serous carcinoma in BRCA?
BRCA1
1-2% risk
Should BRCA1 patients have risk reducing hysterectomy?
Not recommended by any clinical guidelines; may be offerred to patient, may simplify hormone therapy, consider if taking tamoxifen
- if does not change the route of hysterectomy
Can be a discussion with the provider and the patient
What is the cure rate for Stage III-IV ovarian cancer?
18%
What’s the cure rate for Stage I ovarian cancer?
88%
What is the screening for ovarian cancer in average risk women?
NONE TRICK QUESTION YA
What are the outcomes of screening average risk women for ovarian cancer with TVUS?
No mortality benefit
10 women false positive for every 1 case detected
low PPV, harms related to false positives
What symptoms should raise suspicion for screening for ovarian cancer?
> 12 days / month of new symptoms: bloating, pelvic/abdominal pain, early satiety; for <12 months
What other cancers are BRCA carriers at risk for?
BRCA2- Pancreatic, Prostate, Melanoma
BRCA1- uterine
What chromosome is BRCA1 on?
Ch 17
What chromosome is BRCA2 on?
Ch 13
What is recommended ovarian cancer screening in BRCA?
TVUS + CA 125 q6month
short term surveillance starting at diagnosis (annually before age 30) or age 30 until risk reducing surgery
No mortality data for this
What are strategies for risk reduction in BRCA?
OCPs - 10 years of OCP use, 50-64% reduction of risk of ovarian cancer (Iodice et al); even 1 year of use shows significant reduction (Rosenthal et al)
Tamoxifen - mixed data, most useful in preventing contralateral breast cancer after h/o unilateral breast cancer. No impact on ovarian cancer
BSO (reduce by 80%)
Hysterectomy (BRCA1)
What is the benefit of risk reducing OCPs?
reduction of ovarian cancer risk, 33-80% in BRCA1 nad 58-63% in BRCA2 with 1 year of use
Are OCPs associated with breast cancer in BRCA?
No
When should RR BSO be considered for other mutations, not BRCA?
45-50
BRIP1, RAD51C, RAD51D
What is the risk reducing surgery for Lynch syndrome?
hyst-BSO
Age 40-45
What is the effect of risk reducing BSO in BRCA?
reduces risk of ovarian, fallopian tube, or peritoneal cancer by 80%
decreased overall mortality
What is the risk of developing ovarian cancer in BRCA1 by age 40? BRCA2 by age 50?
2-3% BRCA1
3% BRCA2
What is the risk reduction of salpingectomy in the general population?
up to 65%
What is the downside of risk reducing salpingectomy alone?
Second surgery
No protection against breast cancer
What is recommended breast screening in BRCA?
25-29 years: clinical exam q6-12 months and MRI annually
30+ clinical exam, mammo, and breast MRI alternating q6 months
Which has more false positive tests, breast MRI or mammography?
Breast MRI (8-14%) Mammography - 4-15%
What meds are used for chemoprevention of breast cancer?
Tamoxifen
Raloxifene
What is the risk reduction associated with tamoxifen use?
62% risk reduction in BRCA2
No risk reduction in BRCA1 (less ER+ breast cancer in this mutation)
What are the risks of tamoxifen use?
VTE (RR 1.9) and endometrial cancer (RR 2.3)
How much does BSO reduce breast cancer risk?
37%to 90+%
Only if premenopausal at rime of risk reducing surgery
Where should the IP be ligated for risk reducing surgery?
2cm proximal to end of identifiable ovarian tissue
What is the risk of primary peritoneal cancer? (even after risk reducing surgery) in BRCA
1-6%
Frequency of BRCA in the US
1:345
Frequency of BRCA in Ashkenazi Jews?
1:40
Which BRCA is more common in patients with triple negative breast cancer?
BRCA1
How can you test for BRCA?
Single site testing
Targeted multisite testing
Comprehensive gene sequencing
UK-FOCSS study results
Monitor q4 months with CA-125 and TVUS annual
Cancers diagnosed were more often early stage
No survival data - study not mature yet
What is the counseling for fertility options in BRCA?
oocyte or embryo cryopreservation
pre-implantation genetic diagnoses
BRCA1 may be at risk for decreased ovarian reserve
Who should be offered BSO for risk reducing surgery?
BRCA BRIP1 RAD51C RAD51D Lynch (with hyst)
Steps of risk reducing BSO?
Laparoscopic approach Inspect diaphragm and abdominal survey Washings and biopsy Divide tube at insertion of cornua remove 3-4 m of IP ligament remove ovaries separately in bag Serial sectioning on pathology
How much does mastectomy reduce risk of breast cancer by in BRCA?
85-100%
What’s the risk of contralateral breast cancer in BRCA, if has a h/o unilateral breast cancer?
30%
Which BRCA patients can have HRT?
Women with BRCA s/p RRBSO if do not have a breast cancer
Does not diminish RRBSO protective effect
Cowden syndrome
PTEN tumor suppressor
major criteria
minor criteria
Risk of endometrial cancer 19-28%
Risk of breast cancer 25-50% (usually age 30-40)
Peutz-Jeghers
STK11
18-21% of ovarian cancer (sex cord stromal tumor)
44-50% risk of breast cancer
What are STIC lesions?
Serous tubal intraepithelial carcinoma
Pre-invasive lesions
What is seen on STIC path?
p53 overexpression or no expression
increase in the nucleus/cytoplasm ratio, enlarged nuclei with prominent nucleoli, reduction of ciliary cells, loss of polarity, but with no penetration through the basal membrane
What is the risk of primary peritoneal cancer with isolated STIC lesions found in BRCA?
5%
How would you manage a STIC lesion found after BSO?
Consider genetic testing if not already done (if BSO done for other indications)
Discuss completion of staging
appx 15% get chemotherapy, but this is not established
no established role for surveillance
What’s the incidence of STIC in BRCA carriers?
0.6-7%
What is the rate of occult leiomyosarcoma in surgery for presumed fibroids?
1 occult malignancy per 2000 surgeries
(based on meta analysis)
Previously estimated 1 in 500
What are the risks of premature surgical menopause without HRT?
increased overall mortality (total and coronary heart disease)
quality of life
increased osteopenia/osteoporosis
early onset dementia
What are the risks of HRT in BRCA?
HRT does not alter breast cancer risk and does not alter ovarian/breast cancer risk reduction benefuts
What kind of HRT is preferred in BRCA?
estrogen-alone
or intermittent progestin withdrawal or progestin IUD
mild non-significant possible increased breast cancer risk with E+P HRT
What is WHO endometrial schema based on?
glandular complexity
nuclear atypia
has poor intra-observer reproducibility
What is the risk of malignancy with EIN on biopsy?
40%
Asymptomatic woman, what EMB thickness do you sample?
> 11mm
What is the risk of a high-risk uterine cancer (high grade, deep invasion, aka needs staging) in a patient with EIN?
10%
Can a benign gynecologist do a MIS hyst for EIN?
Yes. No need for intra-operatively frozen pathology if no gyn onc available for staging. No routine PPALND for EIN
How effective are LNG-IUDs for EIN or grade 1 endometrial cancer?
88-95% in 2 years
How do you manage EIN medically?
Treat for 6-12 months
Sample q3-6 months until resolution of disease
What is fertility-sparing treatment for endometrial cancer?
D&C if needed to confirm G1 disease
MRI to r/o myometrial invasion
progesterone therapy, resample q3-6 month
If progression, hysterectomy
What are EIN criteria?
Size >1mm
Architecture, grands >55% vs stroma
Cytology - architecturally crowded focus
How much of the uterus does a blind D&C sample?
50%
What is surgical management of EIN
hysterectomy
+/- oophorectomy
peritoneal washings
What is the correlation between frozen adn final pathology for endometrial cancer?
Histology 97% concordant
Grade 88% concordant
Depth of invasion 98% concordant
What progesterones can be used to medically treat EIN?
Provera (medroxyprogesterone acetate) (10-20mg daily)
Depo-Provera (150mg q3 months)
Micronized oral progesterone (200-300mg daily)
Megace (40-160mg daily)
Aygestin (5-15mg daily)
LNG-IUD
What is the risk of endometrial cancer in Lynch synrome?
15-70% depending on mutation
PMS2 - 50%
MLH1 - 20-50%
MSH2/6 - 20-70%
What is the risk of ovarian cancer in Lynch syndrome?
3-40% depending on mutation
MLH1 - 8-20%
MSH2 - 12-38%
Low risk in MSH6 (1-10%) and PMS2 (3-5%)
What are features of Lynch associated endometrial cancer?
Dx young, age 40s-50s
Endometrioid histology
Higher % from lower uterine segment
What are features of Lynch associated ovarian cancer?
Dx earlier, usually Stage I-II
Epithelial or endometrioid type
15-25% have synchronous cancers
How many women with Lynch present with endometrial cancer?
40-60%
What is screening for Cowden syndrome?
Clinical breast exam yearly from age 25
Annual mammogram from age 30
Annual breast MRI from age 30
Annual TVUS or embx from age 30
What is the screening recommended for Peutz-Jeghers Syncrome?
Clinical breast exam q6-12 months from age 25
Mammogram annually
breast MRI annually
Annual pap and pelvic exam from age 20
What are the benefits of RRBSO in BRCA?
Ovarian cancer risk redutcion 96%
Breast cancer risk reduction 50%, more for BRCA1 than BRCA2 (likely earlier, also higher overall risk in brca1)
How do you manage endometrial hyperplasia without atypia?
Progestin therapy (IUD, oral progestin, OCPs)
What is the risk of endometrial hyperplasia without atypica progressing to carcinoma?
less than 10%
What is the median time of regression from endometrial hyperplasia without atypica to normal endometrium?
appx 3 years
What is surveillance for endometrial hyperplasia without atypia being treated with progestins?
Endometrial biopsy q6 months x1 year
If normal endometrium - repeat biopsy not required, may consider continuing tx given risk factors
If persistent EH without atypia - increase dose, repeat biopsy q3-6 months
What is the surveillance for EIN treated medically?
EMBx q3-6 months x2 years
Which two progestins are actually approved for treatment of endometrial carcrinoma?
Provera (medroxyprogesterone acetate)
Megace
What is the benefit of transdermal estrogen replacement?
Lower VTE risk
Lower migraine risk
Theoretically better for libido
what is the appropriate dose of estrogen in hrt
0.625mg conjugated estrogen
1mg estradiol (median starting dose), about half physiologic
50mcg transdermal 17-beta estradiol
What is the dose of progestin replacement for HRT
Provera (5-10mg/day)
Micronized progesterone / Prometrium 100mg/day continuous or 200mg/day cyclic (this is better for lower breast cancer risk, ? greater cardiovascular prevention)
IUD (though not approved)
When can you use OCPs for HRT?
Low risk women in their 40s
bothersome bleeding / hot flashes
still need contraception
What are non hormonal options for control of vasomotor symptoms?
Venlafaxine Fluoxetine Paroxetine Clonidine Gabapentin
What are options for topical vaginal estrogen?
Premarin cream Vagifem tablet (second lowest dose) Estring (lowest systemic dose)
What kinds of breast cancer are more common in BRCA1 vs BRCA2?
BRCA1 - triple negative
BRCA2 - hormone sensitive
What is the data on OCP use for chemoprevention for ovarian cancer?
OCPs reduce ovarian cancer risk in BRCA patients by 50% over 10 years
Systematic review shows reduction with even 1 year of use
Risk reducing salpingectomy benefit?
reduce risk of ovarian cancer by ~60%
