By Krystal Redman (KR), DrPH, MHA, (they/she), Executive Director
In the session entitled Advances in Pregnancy-Associated Breast Cancer, Dr. Kalliopi Siziopikou, MD, PhD, of Northwestern University, provided a presentation titled Updates in the Pathology of Pregnancy-Associated Breast Cancer (PABC).
Pregnancy-associated breast cancer (PABC) is defined as breast cancer diagnosed during gestation, lactation, or within 1 to 5 years postpartum. While the development of malignancy during pregnancy is rare, the incidence is increasing. Breast cancer is one of the most common cancers diagnosed during pregnancy and the postpartum period, occurring in up to 1 in 3000 deliveries (Smith et al., 2001; Donegan, 1983; Pavlidis, 2002). [This means that 1 of 3,000 pregnancies is complicated by the development of breast cancer.] Keep in mind, breast cancer is the leading cause of cancer death in the US for cis women in the age group of 15-29 years.
Approximately 1 in 5 breast cancers among women who are 25-29 years old is diagnosed either during pregnancy or during the first postpartum year. This age range may increase in the future as people delay childbearing. Pregnancy has a dual effect on breast cancer development: on one hand, pregnancy is protective from cancer and on the other, it is cancer-promoting. While a number of hypotheses have been proposed over the years to explain these effects, the most likely hypothesis for the development of PABC is the involution hypothesis. [Involution – the shrinkage of an organ in old age or when inactive, e.g. of the uterus after childbirth.] This hypothesis proposes that the involution pathways activated during pregnancy and the immediate postpartum period are remodeling programs similar to wound healing and inflammation that may be associated with tumor development and progression.
Although PABCs can be any subtype of breast carcinomas, they are usually invasive ductal carcinomas [the presence of abnormal cells inside a milk duct in the breast] of high tumor grade and large tumor size with higher stage at presentation and higher rates of lymph node involvement. Most PABCs are hormone receptor negative tumors with high Ki-67 [aggressive tumor growth] proliferation rates; most frequently, they are either triple negative or HER2-positive carcinomas. A number of studies have shown that PABCs have different genomic signatures than the non-PABC tumors with PABCs having an increased expression of immune response mediators. Better understanding of the molecular pathways of tumor initiation and progression and prompt diagnosis and state-of-art treatment protocols in PABC are expected to lead to better outcomes for these young breast cancer patients.
Dr. Siziopikou suggests that older terminology grouping all pregnancy-associated breast cancer (pregnancy breast cancer [PrBC], and postpartum breast cancer [PPBC]) is outdated and should no longer be used. Rather, PABC should be separated into 2 categories. She notes that science should separate the definitions in order to aid in providing better management strategies and to recommend treatment that is in the best interest of both the pregnant person and the fetus, but Dr. Ann Partridge, MD, MPH, of the Dana-Farber Cancer Institute, boldly challenged this recommendation. In Dr. Partridge’s session entitled Special treatment issues in this young patient population she stated that PABC should not be categorized as categories can overlap. For instance, you can be diagnosed with breast cancer while postpartum and also be pregnant with your next baby.
Dr. Partridge notes that breast cancer in young patients is complicated. But breast cancer during pregnancy (PrBC) is REALLY complicated. A pregnant person may experience pregnancy complications apart from breast cancer, e.g. preeclampsia. And if a patient is experiencing non-breast cancer related complications in pregnancy, this may influence the ability to move forward with possible treatment and/or management strategies. For instance, if a pregnant person has preeclampsia and they wish to undergo surgery as a treatment option, they may not be a candidate for surgery due to possible severe risks of complications, including death as an outcome of undergoing surgery while preeclamptic.
Treatment and management of PrBC requires a multidisciplinary team. During the session, it was stated that “mammography and MRIs are ‘pretty safe’ during pregnancy” and that there is not a great concern with waiting for surgery while pregnant as miscarriages are common among all pregnant people. Breast cancer diagnosis does not change this. And surgery and anesthesia do not necessarily cause miscarriage. Pre-op Her2 therapy would require a consideration to end the pregnancy. Questions that immediately come to mind are: Wiith the overturn of Roe v. Wade, are there any potential barriers to abortion care if the patient chooses to end their pregnancy to begin breast cancer treatment? What if the pregnant person lives in a state where anti-abortion laws are in place? In this case, will the patient have to travel to continue care with another provider who is not a part of their treatment or care team? Let’s not even discuss the financial implications of this – treatment and costs associated with ending a pregnancy – if that in fact is what the patient chooses.
Patients with PrBC may have a number of potential complications. These complications may result from chemotherapy, endocrine therapy, local therapy, poor psychosocial functioning, issues with sexual health and body image, challenges with role functioning, fertility problems and premature menopause, etc.
Complex therapeutic and ethical challenges must be considered as well. For example, while the pregnant person is the beneficiary of treatment, the fetus may be put at risk. Safety and efficacy data from randomized clinical trials are limited. Where available, the sample sizes in the clinical trials are small and the trials are often not randomized for ethical reasons. Therefore, most of the data that informs treatment options comes from case reports or observational cohort studies, which are subject to variable quality, heterogeneity, and bias.
Sometimes, standard treatment algorithms may need to be modified to aim for the most effective treatment for the patient while minimizing toxicity for the fetus. However, what if the patient decides not to pursue any treatment until after the birth of their baby? What management recommendations would be made then?
Individualizing breast cancer care in pregnancy requires balancing the risks to the fetus, such as adverse effects of chemotherapy, surgery, radiation, hormones, targeted therapy, etc. against the risks to the pregnant person, such as effects of the cancer and loss of pregnancy. Other important factors to consider when making treatment choices include the disease phenotype and stage, pregnant person’s gestational age, and patient preferences. Ultrasound is usually the first choice of imaging. If negative, then a mammogram would be indicated. Surgery is generally safe starting at 8-12 weeks of gestation. It’s important to have a multidisciplinary consultation at time of first contact before proceeding with lumpectomy especially because of the mandatory delay in initiation of radiotherapy.
Pediatric outcomes after maternal breast cancer diagnosis and treatment were reported in a study that recruited 129 children from PrBC patients (75% with chemo exposure) and 129 control children. Starting in infancy, the authors assessed the childrens’ general health, cognitive function, and cardiac status longitudinally. 61% of neonates in the PrBC group were born preterm (< 37 weeks) vs. 8% in the general population. Cognitive function significantly improved with each extra week of gestation in both groups and there was a trend towards lower birth weight for PrBC, but with a “catch-up” after delivery. No structural cardiac abnormalities were seen on follow-up echo at age 3 years.
In conclusion, many of the commonly used diagnostic tests are safe for both the pregnant person and the fetus. This includes X-Rays, MRI, CT scans, ultrasounds and biopsies. X-Rays and CT scans, however, should be used with caution due to the radiation. The radiation produced from X-Rays has been proven to be too low to cause harm to a fetus. Despite this finding, many doctors continue to recommend a lead shield to cover the abdomen for added caution. CT scans, on the other hand, give off a higher quantity of radiation. A CT scan of the head or neck is perfectly safe for all parties involved. Scans of the pelvis or abdomen should only be done if absolutely necessary and after a discussion with the health team (nfcr.org, Dec 2022).
If the investigations result in a cancer diagnosis, both the obstetrician team and the oncology team will work together to decide the best options for treatment. Both surgery and chemotherapy can be safe for the pregnant patient and the fetus. The health team will consider many factors, including the type, location, size, and stage of the cancer. Depending on these factors, the woman may be able to receive treatment immediately. Depending on the drug, the health team may recommend waiting until after the first trimester (when the baby’s organs are developed) or waiting until after the birth to start chemotherapy.
With a knowledgeable care team, cancer rarely affects the baby during pregnancy. If administered in the first trimester, chemotherapy may cause birth defects or pregnancy loss. Administering chemotherapy after the first trimester has far less severe risks, the most important being possible preterm birth and the possibility of babies being small for gestational age. While these are important risks to be aware of, they are not necessarily common. Once the baby is born, the patient can continue with treatment. If receiving chemotherapy, however, breastfeeding is not recommended.
For patients diagnosed with breast cancer during a pregnancy, the goals of therapy are to conform as closely as possible to standardized protocols; however, this often involves an element of compromise.
The prognosis of people with PrBC appears to be the same as that of non-pregnant controls as long as appropriate systemic therapy is provided. Practitioners can “successfully” perform surgery with sentinel lymph node biopsy and interventional radiology, provide chemotherapy, but cannot generally recommend tamoxifen, trastuzumab, radiotherapy, or other newer therapies (IO, PARPi, CDK 4/6 inhibitors, etc.) These recommendations require a multidisciplinary team approach which may include: radiology, pathology, surgical oncology, plastic surgery and radiation oncology, medical oncology, pharmacy, maternal fetal medicine (high-risk obstetrics), neonatology, nursing, social work, psychosocial oncology, ethical, legal, practical, and spiritual support, for the patient and their loved ones.
When discussing the multidisciplinary team, one common theme I noticed was mentioning the patient as a part of the team at the very end as if “the patient” is the least important part of the team. And many times the patient was not mentioned at all when discussing treatment decision making. The patient is, in fact, the leader of the multidisciplinary team and should lead all decisions related to their diagnosis, management, treatment, or non-treatment. Pregnancy, with the choice of carrying, already affects the person’s body, mind, psychosocial functioning, emotions, and much more. Adding a breast cancer diagnosis into the mix further complicates it. Regardless of your breast cancer diagnosis, the patient has reproductive freedom to make whatever decision they wish around their pregnancy and body.
Matters to note: The study only looked at cis women pregnancy breast cancer [PrBC], and postpartum breast cancer [PPBC].