1. Breast Cancer in Pregnancy
Tricia Merrigan, MD, FACS
Avera Medical Group
Comprehensive Breast Care
September

2. Outline Introduction Epidemiology and risk factors Diagnostic work up
Treatment of breast cancer in pregnancy
Staging
Treatment options
Special considerations in pregnancy
Obstetric follow-up during treatment

3. Introduction
Breast cancer is the most common cancer among women both in the US and in the world
About 1 in 8 women (12%) will be diagnosed with an invasive breast cancer during their lifetime
In 2015, an estimated 231,840 new cases of invasive breast cancer are expected to be diagnosed in women in the U.S., along with 60,290 new cases of non-invasive (in situ) breast cancer

4. Introduction
About 2,350 new cases of invasive breast cancer are expected to be diagnosed in men in 2015
A man’s lifetime risk of breast cancer is about 1 in 1,000
In 2015, there are more than 3 million breast cancer survivors in the US
Because of early detection and improvements in treatment, there were more than 2.6 million….

5. Breast Cancer in Pregnancy
Pregnancy-related breast cancer is defined as breast cancer diagnosed during pregnancy or within 1 year after delivery
Breast cancer occurs about once in every 3,000 pregnancies
3.9 million births in U.S. in 2014
1300 cases of breast cancer estimated in pregnancy
Because of early detection and improvements in treatment, there were more than 2.6 million….

6. Breast Cancer in Pregnancy
Typically presents as a painless lump palpated by the woman
Often diagnosed at a later stage
Women who are pregnant or nursing often have swollen and tender breasts making it more difficult to identify masses
This leads to poorer outcomes than breast cancer in non-pregnant women
Clinical breast exams should be part of prenatal and postnatal care

7. Risk Factors for Breast Cancer
General population–
Established Risks:
being female and growing older
Family history
Women with a mother or sister with breast cancer are at about a 2-fold risk
85% of women diagnosed WILL NOT have a family history
5-10% are truly hereditary (i.e. BRCA mutation, PTEN, P53)
Reproductive factors
Age at menarche, parity, age at first pregnancy, age at menopause, breastfeeding history, exogenous hormones
2 out of 3 newly diagnosed invasive cancers are in women 55 or older compared to 1 out of 8 for women under 45

8. Risk Factors for Breast Cancer
Lifestyle and dietary factors
Obesity, alcohol use, smoking, lack of exercise
Breast factors
Dense breasts
Previous biopsies with moderate to high risk pathology
Enviromental
Prior thoracic radiation
Risk highest if before 20 and lowest if after 40
Women with dense breasts have a 2- to 6- fold increase
Nonproliferative (fibroadenomas, cysts)- none to small
Proliferative without atypia (adenosis, intraductal papilloma) to 1.9-fold increased risk
Proliferative with atypia (ADH, LCIS)- 3- to 5-fold increased risk

9. Risk Factors
No specific risk factors for breast cancer in pregnancy are known
BRCA1 or BRCA2 mutations may be at increased risk, but they do not have an increased incidence of breast cancer in pregnancy
As women defer childbearing and the incidence of malignancies rises with age, this situation is expected to become more common
The longer we live, the more oppurtunities there are for genetic damage to the cells.

10. Diagnostic Work Up History and physical Clinical breast exam
Any suspicious breast lump or inflamed breast needs evaluation
Presumed mastitis that does not resolve with initial treatment should prompt evaluation
Ultrasound preferred first
Bilateral Mammography (shielded)

11. Diagnostic Work Up
If diagnostics are negative consider referral to specialist
If positive, then continue with biopsy (core biopsy preferred)
**A percutaneous biopsy of any lesion that does not meet all the criteria for a simple cyst is strongly recommended**
Also recommend that you communicated with pathology that the patient is pregnant which can avoid over-interpretation of pathology

12. Breast Cancer in Pregnancy

13. Breast Cancer in Pregnancy
Two main types of breast cancer
Invasive ductal- 80% of breast cancer cases
Invasive lobular- 10% of breast cancer cases
Inflammatory breast cancer is a clinical diagnosis when the breast cancer blocks the lymphatics and causes a red, swollen, “inflamed” breast
Very aggressive and progresses rapidly
Accounts for 1-6% of all breast cancers in the US

14. Breast Cancer in Pregnancy
Most pregnant patients are diagnosed with invasive ductal carcinomas which are often associated with aggressive behavior
Grade 3 tumors
Lymphovascular invasion
High rate of estrogen receptor negativity
About 42% HER2 positive

15. Breast Cancer in Pregnancy

16. Staging of Breast Cancer in Pregnancy
Early stage breast cancer (T1-T2, node negative cancers)
CXR with shielding
CBC, CMP
T3-T4 tumors or node positive disease
US liver
Consider MRI thoracic/lumbar spine wo contrast
Can also consider bone scan with foley catheter
If later in pregnancy, consider staging with CT/bone scan
after delivery

17. Treatment of Breast Cancer in Pregnancy
Treatment should involve a multidisciplinary care team including organ system specialists, oncologists, obstetricians, perinatologists, pediatricians, and psychologists
Every patient with cancer during pregnancy should be recorded in a registry to provide information about medical management

18. Treatment of Breast Cancer in Pregnancy
The goal is to provide accurate information and define when and how far to push back usual treatment limits to satisfy the patient’s wishes while thinking about oncologic risks

19. Treatment of Breast Cancer in Pregnancy
Lumpectomy + radiation
Timing depends on biology of tumor, gestational age, need for chemotherapy (either Neo or adjuvant)
Mastectomy w/wo reconstruction w/wo radiation
Sentinel lymph node biopsy is safe in pregnancy
Use sulfur colloid technetium 99 or Lymphoseek
No lymphazurin or methylene blue

20. Treatment of Breast Cancer in Pregnancy
Body
Chemotherapy- Can be given in 2nd and 3rd trimester with approved drugs
Often given in neoadjuvant (before surgery)
Especially in triple negative, Her2 positive, or locally advanced (lymph node metastasis)
If Er+(node neg), often Oncotype DX or Mammaprint gene assays used to determine chemotherapy benefit
Endocrine therapy- Antiestrogen therapy is delayed until after delivery

21. Treatment Algorithm <12 wks

22. Treatment of Breast Cancer in Pregnancy <12 weeks
Special considerations
Prefer delaying surgery if possible until 2nd trimester
Chemotherapy is contraindicated in 1st trimester, but considered relatively safe in 2nd and 3rd
Her2 based therapy contraindicated during pregnancy
Maximum timeframe from surgery to radiation (if chemotherapy not recommended) that is considered safe is about 20 weeks

23. Treatment Algorithm 12-28wks

24. Treatment Algorithm >28wks

25. Treatment of Breast Cancer in Pregnancy
Other considerations
Fertility- If undergoing chemotherapy, consider referral to fertility specialist for discussion about risks and options
Pregnancies after breast cancer treatment
New data suggests that it is safe for patients to become pregnant 2 years after completion of treatment for breast cancer

26. Obstetric Follow-up During Treatment
Fetal monitoring before and after surgery
Chemotherapy
Check for fetal wellbeing and general development
Check for preterm contractions
Check for intrauterine growth restriction
No chemotherapy after 35 weeks
Delivery
Mode of delivery determined by obstetric indications
Preferably after weeks gestation
At least three weeks after last cycle of chemotherapy
If preterm delivery is inevitable, fetal lung maturity if essential

27. Obstetric Follow-up During Treatment
Post-partum
Examine placenta for metastatic disease
Oncological treatment can be continued immediately after
vaginal delivery and a week after uncomplicated C-section
Breastfeeding
Contraindicated during and after chemotherapy

28. Conclusions
Breast cancer occurs in about 1 out of every 3000 pregnancies.
Often diagnosed at a later stage with aggressive disease.
Breast cancer treatment during pregnancy is possible and termination of pregnancy is not likely to improve prognosis.
Multidisciplinary team is a must.
Timing of pregnancy determines different treatment options.
Chemotherapy can be administered in 2nd and 3rd trimesters.
Registries are necessary to accrue numbers that allow more robust conclusions.

29. Sources NCCN Guidelines Version 2.2015- Breast Cancer- www.nccn.org
Amant et al. Breast Cancer in Pregnancy. Lancet. 2012;379(9815):
Morice, P, Uzan C, et al. Lancet. 2012;379(9815):
Kuerer, H. M. (2010). Kuerer’s Breast Surgical Oncology. China: The Mcgraw-Hill Companies, Inc.Philippe Morice, Catherine Uzan, Serge Uzan Philippe Morice, Catherine Uzan, Serge Uzan

30. THANK YOU!!
Questions?