We learn more about pregnancy associated breast cancer (PABC).
Breast cancer (BC) is the most common malignancy in pregnancy. It occurs at a rate of 1 in 3 000 pregnancies. Pregnancy associated breast cancer (PABC) is defined as a cancer diagnosed during pregnancy, up to one year post delivery and during lactation. The average age of presentation is between 32 and 38. BC is not caused by pregnancy but occurs coincidently with pregnancy.
Unravelling risk factors… not possible
Early first pregnancy is supposed to confer protection against BC. Remember, most women with BC (65%) have no significant risk factors. Having a first pregnancy over 35 years is an increased risk. A recent study shows for 10 years post pregnancy women are at an increased risk.
Women with BRCA- 1 and 2 mutations may be at increased risk of BC if their first pregnancy is under 40. The incidence of PABC is higher in BRCA 1 mutations than BRCA 2. So, this means anyone is at risk, hence a routine breast ultrasound during pregnancy is worthwhile.
Anatomical and physiological changes in pregnancy
Due to increased levels of oestrogen, progesterone, prolactin and chorionic gonadotropin, there is marked lobular alveolar growth, marked ductal and lobular proliferation, engorgement of blood vessels and increased mammary blood flow. All of this makes clinical and mammographic assessment of the breast in pregnancy difficult. Thus, ultrasound is the mainstay of assessing.
Delays in diagnosis are common, and occur in late patient discovery of the mass, and due to clinician failure in asking for needle biopsies, and general assumptions that the diagnosis is benign.
Physicians involved in obstetrical care should play a major role in the diagnosis starting from pre-pregnancy ultrasounds in elderly women who are pregnant for the first time, to thorough breast examinations and ultrasound at the initial visit (particularly if the breast is difficult to assess due to nodularity). This baseline study at a time when the pregnancy associated physiological changes are minimal is essential.
The delays in diagnosis contribute to the more advanced disease at presentation and to the misunderstanding that PABC has a worse prognosis. Screening mammograms are not routinely performed mainly due to the fact that these women fall under the age for routinely recommended mammogram (they can be performed with little risk to the foetus).
The main problem, however, is the increased density of the breast tissue, resulting in a higher false negative finding on a mammogram. A breast ultrasound is safe, accurate and provides a rapid differentiation of cystic and solid masses. The value of a triple assessment in pregnancy is essential and all masses that are dominant and palpable should undergo a needle biopsy.
The goal in pregnant women with breast abnormalities is to make the diagnosis accurately with the least invasive technique possible. A core biopsy is highly accurate with minimal risk of milk fistula formation.
There are many treatment options. Treatment should not be delayed because of the pregnancy, and women should be treated mainly according to the guidelines of non-pregnant women with the modification of protection of the foetus. The most critical aspect is a multi-disciplinary team that can discuss options with the patient and her family. Informed consent is important.
The risk to the foetus and possible maternal benefits must be considered. Pregnancy associated breast cancer is a complicated psychosocial issue. Abortion is usually not recommended and has no bearing on patient survival (some studies have even found that women who terminate may have a worse outcome).
These factors should be assessed before termination is considered: the patient’s prognosis (huge strives have been made in ensuring long disease free intervals for women with BC); the ability to cope with a new infant; the effect of multimodal treatment on the foetus; and the possible consequences of maternal and foetal death. An important aspect is regular prenatal monitoring during therapy by serial foetal ultrasounds. Close attention should be paid to gestational age. Remember, BC treatment is based on biology today.
Local treatment options
Breast and axillary surgery can be performed during any trimester of pregnancy as long as specialist physicians and anaesthetists are monitoring for the special physiological changes in pregnancy.
The old adage that the surgery of choice is a modified radical mastectomy as it avoids the inherent risk of radiation exposure associated with breast-conserving surgery is really not necessary. Breast conservation can be done with delaying the radiation to post delivery. Breast reconstruction can be done at the time of breast surgery. All these patients should be managed in units that routinely offer immediate reconstruction; as well as having a special interest in PABC. A direct implant reconstruction, with nipple-saving, or a tissue expander may be inserted at time of mastectomy.
Radiation is still contraindicated during pregnancy and although isolated studies have used radiation during pregnancy, neo-adjuvant therapy can be given during the second trimester. A sentinel lymph node biopsy may be undertaken with caution in these patients as there are no studies on the safety of the dye in pregnancy though feotal exposure to the isotope is considered low.
Systemic therapy options
Chemo is generally not given in the first trimester as this is when development of bodily organs occurs. Waiting to start treatment in the second trimester is safer. Taking a few weeks to assess all options and go for second opinions is recommended.
Chemo drugs can be used during pregnancy without undue complications of harm to the foetus. Chemo should be avoided for two weeks prior to delivery. Again specialist obstetric units should treat these women and be involved in the delivery options and safety. Studies have confirmed minimal chemo long-term affects to these children; with the commonest effects of chemotherapy being babies born ‘small for gestational size’. Treatment with tamoxifen or aromatase inhibitors should be delayed until the completion of pregnancy with care taken to deep vein thrombosis risk post pregnancy.
The initial assumption that PABC patients do poorly has been attributed to late presentation. Actually, the prognosis is identical to that of the non-pregnant woman.
The recommendation is to wait two years between ending treatment and future pregnancies. This is purely because of a higher rate of relapse and recurrence during the first two years of all women with BC. Subsequent pregnancies don’t negatively affect prognosis of early BC although the concerns and difficulties of conception due to cytotoxic agents must be addressed.
MEET OUR EXPERT – Prof Carol-Ann Benn
Prof Carol-Ann Benn heads up internationally accredited, multi-disciplinary breast cancer centres at Helen Joseph Hospital and Netcare Milpark Hospital. She lectures at Wits University and, in 2002, established the Breast Health Foundation.