Breast cancer

Question 1

Outline the investigations you would organise in a woman with a breast lump during pregnancy suspicious for breast cancer:

Answer 1

• Breast ultrasound: to assess discrete lump
• If cancer confirmed, mammography (with fetal shielding) to assess the extent of the disease and the contra lateral breast
• Ultrasound-guided biopsy: histological grade, receptor status, HER2 status. Histology rather than cytology because the proliferative change during pregnancy renders cytology inconclusive

Staging imaging:

• CXR
• Liver ultrasound
• Consider gadolinium MRI if bone invovlement suspected; limited data but not evidence of adverse outcomes for fetus.

Question 2

List potential management plan for breast cancer treatment during pregnancy:

Answer 2

• Referral to breast cancer MDM.
• Termination of pregnancy an option after careful consideration.
• Surgical loco-regional clearance.
• Sentinel node assessment +/- axillary clearance.
• Radiotherapy: only if life-saving or to preserve organ function e.g. spinal cord compression.
• Systemic chemotherapy: contraindicated in first trimester but safe in second trimester.
• Delivery: usually full term.

Question 3

What are the principles of surgical management of breast cancer in pregnancy?

Answer 3

• Loco-regional clearance
• Can occur in all trimesters.
• Reconstruction delayed till after pregnancy: avoid prolonged anaesthesia and allow optimal symmetrisation of breasts.
• Sentinel node assessment: radioisotope scintigraphy okay in pregnancy but avoid blue dye as effect unknown.

Question 4

What are the principles of radiotherapy treatment of breast cancer in pregnancy?

Answer 4

• Routine breast and chest wall radiotx should be deferred till after pregnancy.
• Contraindicated unless life-saving or to preserve organ function.
• If used in pregnancy, use fetal shielding or consider early elective delivery depending on gestation.

Question 5

What are the principles of chemotherapy treatment of breast cancer in pregnancy?

Answer 5

• Contraindicated in first trimester due to high rate of fetal anomalies.
• Safe in second trimester: athracyline regiments. No evidence of increased miscarriage, IUGR, organ dysfunction or long-term adverse outcomes.
• Not safe in pregnancy: tamoxifen and trastuzumab.
• G-CSF can be used in pregnancy to reduce neutropenia complications for mum and fetus.

Question 6

When should baby be delivered when mum is receiving treatment for breast cancer?

Answer 6

• Majority at full term (normal or IOL).
• If early elective delivery indicated, consider antenatal corticosteroids depending on gestation.
• Wait 2-3 weeks after last chemotx to reduce neutropenic complications.

Question 7

Outline the principle considerations regarding breastfeeding and chemotherapy and other treatment for breast cancer:

Answer 7

• Breastfeeding while on chemotherapy is not advised as baby at risk of neutropenia and infection.
• Wait 14 days or more between last chemotherapy and starting breast feeding.
• Drugs not safe while breastfeeding: tamoxifen, trastuzumab.
• A short period of breastfeeding prior to starting chemotherapy may be mentally beneficial for mother and baby.

Question 8

Outline the principle considerations regarding contraception in a woman with breast cancer:

Answer 8

• Use non-hormonal contraceptive methods.
• Hormonal contraception may be considered after at least 5 years free of recurrence.
• Mirena may reduce risk of endometrial hyperplasia and malignancy in tamoxifen users but further evidence regarding safety in breast cancer survivors is needed.
• Discuss any choice of hormonal contraception with breast surgeon first.

Question 9

Outline your discussion with a breast cancer survivor regarding future pregnancy planning:

Answer 9

Women should be seen by clinical oncologist, breast surgeon and obstetrician.

Advise no evidence of increased congenital malformations or stillbirth after treatment.

Women should wait 2 years after diagnosis and treatment before conceiving as risk of recurrence highest in first 2 years.
- ER positive disease: should complete 5 years of tamoxifen

If metastatic disease: advise not to become pregnant due to limited life expectancy and compromising treatment.

Preparing for conception:

• Stop tamxiofen 3 months before trying.
• Complete routine imaging.
• If BRCA positive, offer preimplantation genetic diagnosis.

Question 10

What special considerations and care is needed during pregnancy following treatment of breast cancer?

Answer 10

• MDT care under obstetrician, oncologist and breast surgeon.
• ECHO: if had anthracycline chemotherapy (doxirubicin, epirubicin) which can cause dose-dependent left ventricular dysfunction and cardiomyopathy.

Counsel:
- Slightly increased risk of delivery complications (OR 1.5) and CS (OR 1.3).
- Can breastfeed from unaffected breast.
- Radiotherapy causes fibrosis and lactation unlikely.
Should have lactation support.

Question 11

How does pregnancy impact prognosis for women diagnosed with breast cancer during pregnancy?

Answer 11

It does not worsen prognosis.

As pregnancy associated breast cancer occurs in a YOUNGER population who may have FEATURES that carry a higher risk of metastasis such as high grade tumours and oestrogen receptor negative tumours, these younger women may be expected to have an inferior prognosis.

Question 12

In breast cancer survivors, how does pregnancy impact prognosis?

Answer 12

It does not worsen prognosis.
Survival at 5 years: 92%
Survival at 10 years: 86%.

Question 13

Outline management principles of fertility in women diagnosed with breast cancer:

Answer 13

Referral to fertility specialist.

Effect of treatment on fertility should be discussed:

• Adjuvant chemotherapy: amenorrhoea, cycle irregularity, subfertility. Depends on age (>35yrs 50% amenorrhoea vs. <5% if <30 yrs), chemotx drug/dose (MTX, 5-FU more gonadotoxic than anthracycline)
• Adjuvant hormonal therapy: tamoxifen (irregular cycles, endometrial pathology), GnRH analogue (amenorrhoea, oestrogen deficiency sx)

Options for fertility preservation and conception in the future should be discussed:

• Egg donor with short-term HRT.
• Replacement of cryopreserved embryos with HRT
• Surrogacy

Note: HRT carries theoretical risk of hyperestrogenism.

Question 14

What issues are there with cryopreservation in a woman recently diagnosed with breast cancer?

Answer 14

• Time taken for cryopreservation may delay chemotherapy.
• Long term risks of ovarian stimulation for egg and embryo freezing is unknown.
• Elevated oestrogen levels may be deleterious in ER positive breast cancer.

Question 15

You are seeing a woman who has had breast cancer treated in the past. She is BRCA carrier positive and desires fertility.

Outline your counselling and management to her regarding fertility:

Answer 15

• BRCA gene is a tumour suppression gene with autosomal dominant inheritance meaning there is a 50% chance one of her children would also be a carrier.
• Positive carrier status is associated with an increased risk of breast cancer (40-80%) and ovarian cancer (10-20% if BRCA2, 40-60% if BRCA1).
• Option for PIGD: involves IVF then testing of a few cells from embryos to select those that do not carry the gene.
• Cons: HRT may have a negative effect on breast cancer outcome; IVF and/or implantation may not be successful; OHSS; expensive and stressful.

Other options:

• Surrogacy
• Egg donor with HRT

Long-term management of BRCA carrier:

• Double mastectomy
• rrBSO when family complete: surgical menopause. Systemic HRT contraindicated. Mgmt: topical oestradiol, clonidine/gabapentin for vasomotor sx, bisphosphonates for osteoporosis prevention.