Review

Cancer and Pregnancy in the Post-Roe v. Wade Era:

A Comprehensive Review
Ganguly Arup 1, * and Narmala Shravan 2

1 Department of Internal Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA
2 Department of Hematology and Oncology, DHR Health Oncology Institute, Edinburg, TX 78539, USA;
s.narmala@dhr-rgv.com
* Correspondence: ganguly@uchc.edu; Tel.: +1-860-679-8025; Fax: +1-860-679-4613

Abstract: Cancer during pregnancy, affecting 1 in 1000 pregnancies, is rising in incidence due to
delayed childbearing and improved detection. Common types include breast cancer, melanoma and
cervical cancer and Hodgkin’s Lymphoma. There are several physiological changes that occur during
pregnancy that make its management a challenge to clinicians. Managing it requires multidisciplinary
approaches and cautious test interpretation due to overlapping symptoms. To minimize fetal radiation
exposure, non-ionizing imaging is preferred, and the interpretation of tumor markers is challenging
due to inflammation and pregnancy effects. In terms of treatment, chemotherapy is avoided in the first
trimester but may be considered later. Immunotherapy’s safety is under investigation, and surgery
depends on gestational age and cancer type. Ethical and legal concerns are growing, especially with
changes in U.S. abortion laws. Access to abortion for medical reasons is vital for pregnant cancer
patients needing urgent treatment. Maternal outcomes may depend on the type of cancer as well
as chemotherapy received but, in general, they are similar to the non-pregnant population. Fetal
outcomes are usually the same as the general population with treatment exposure from the second
trimester onwards. Fertility preservation may be an important component of the treatment discussion
depending on the patient’s wishes, age and type of treatment. This article addresses the complicated
nature of a diagnosis of cancer in pregnancy, touching upon the known medical literature as well
as the ethical–legal implications of such a diagnosis, whose importance has increased in the light of
recent judicial developments.

Keywords: pregnancy; abortion; cancer; immunotherapy; Roe v. Wade; chemotherapy

Citation: Arup, G.; Shravan, N.
Cancer and Pregnancy in the
Post-Roe v. Wade Era: A
Comprehensive Review. Curr. Oncol. 1. Introduction
2023, 30, 9448–9457. https://doi.org/ Cancer during pregnancy poses unique challenges to maternal and fetal well-being.
10.3390/curroncol30110684 Pregnancy-Associated Cancers (PAC) are defined as cancers diagnosed in the pregnancy
Received: 10 October 2023
and/or the post-partum period. Published data indicate that such cancers occur in ap-
Revised: 22 October 2023 proximately 1 in 1000 pregnancies [1]. The most common malignancies during pregnancy
Accepted: 23 October 2023 include breast cancer, melanoma, cervical cancer, lymphomas, and leukemias. The in-
Published: 25 October 2023 creasing prevalence of cancer during pregnancy, influenced by delayed childbearing and
improved detection, emphasizes the need for optimized care. Obtaining an accurate di-
agnosis while minimizing fetal harm is a delicate balance, involving multidisciplinary
approaches and the cautious interpretation of tests [2].
Copyright: © 2023 by the authors.
Following the emergence of targeted therapy and newer treatments, as well as the
Licensee MDPI, Basel, Switzerland.
establishment of clear guidelines to allow for a more standardized approach, can ensure
This article is an open access article
the best outcomes for both mother and child.
distributed under the terms and
Ethical considerations involve respecting maternal autonomy and optimizing out-
conditions of the Creative Commons
comes through shared decision-making and open communication. This review focuses
Attribution (CC BY) license (https://
on enhancing cancer management in pregnancy, covering the diagnosis, treatment con-
creativecommons.org/licenses/by/
4.0/).
siderations, surveillance, and ethical complexities, and discussing the implications of

Curr. Oncol. 2023, 30, 9448–9457. https://doi.org/10.3390/curroncol30110684 https://www.mdpi.com/journal/curroncol

Curr. Oncol. 2023, 30 9449

the overturning of the Roe v. Wade ruling on access to cancer treatment for pregnant
individuals.

2. Epidemiology and Risk Factors

The prevalence of cancer during pregnancy is increasing, and these patients are
at increased risk for poor outcomes. According to a recent nationwide study from the
National Inpatient Sample, the prevalence rate of pregnancy with cancer was 69.3 per
100,000 deliveries and increased from 64.5 to 73.4 between 2016 and 2019 (relative increase,
13.8%; p < 0.001) [3]. Cancer was associated with a range of factors, including patient
characteristics such as advanced age, a more recent year of delivery, White ethnicity,
obesity, smoking, preexisting hypertension, and exposure to chemotherapy. Additionally,
pregnancy characteristics like early preterm delivery and cesarean delivery were also linked
to cancer. Table 1 shows the incidence of various types of cancer commonly associated with
pregnancy in the population of the United States [4–13].

Table 1. The incidence of various cancers in pregnancy per 100,000 pregnancies.

Type of Cancer Incidence Per 100,000 Pregnancies

Breast cancer 33
Cervical intraepithelial neoplasia 200
Cervical cancer 1–120
Hodgkin’s lymphoma 16–100
Non-Hodgkin’s lymphoma 1–5
Leukemia 1
Ovarian cancer 3–6
Melanoma 39
Thyroid cancer 14
Colorectal cancer 2
Head and neck (non thyroid) 0.7

3. Diagnostic Challenges
3.1. Impact of Pregnancy on Cancer Diagnosis
Pregnancy involves a change in the physiology of the body and has a high metabolic
demand, which is amplified by the detection of a cancer. The physiological changes that
occur during pregnancy may contribute to the masking of cancer symptoms [14]. There
are several overlapping signs and symptoms of cancer and pregnancy, including nausea
and vomiting, appetite changes, constipation, abdominal discomfort, anemia, a palpable
breast mass/increased volume and consistency of breast tissue, hyperpigmentation, and
fatigue [15,16]

3.2. Considerations for Imaging Modalities and Radiation Exposure

It is important to select appropriate imaging studies that minimize stress and avoid
the unwanted termination of pregnancy. Non-ionizing modalities such as ultrasound (US)
and Magnetic Resonance Imaging (MRI) are considered first-line options. When Computed
Tomography (CT) scans are used, radiation dose and subsequent fetal dose should generally
not exceed 0.10 Gray (Gy) [17]. CT of the head, neck, thorax, and extremities is generally
considered safe. PET/CT and PET/MRI are used for staging and assessing treatment
response [18]. Since PET/CT involves both radioisotopes and CT, it results in a higher total
radiation dose compared to CT alone. Therefore, the use of PET/CT should be carefully
considered in pregnancy. On the other hand, a PET/MRI is another viable modality, with
early studies showing some benefit [19,20]. A fetal dose of 0.1 Gy carries a small individual
Curr. Oncol. 2023, 30 9450

risk of radiation-induced cancer, but more than 99% of exposed fetuses will not develop
childhood cancer or leukemia [18].
Several radioisotopes are considered unsafe in pregnancy. Some of them may cross
the placenta and remain in the fetus for several days and can cause organ damage [18]. In
general, therapeutic radiopharmaceuticals should be avoided during pregnancy, except in
cases where the mother’s life is at risk. In such situations, careful assessment of the fetal
dose and gestational age (GA) may be necessary, and the possibility of the termination of
pregnancy should be considered.

4. Challenges in Interpreting Tumor Markers during Pregnancy

Specific tumor markers are produced not only by tumor cells but also in response
to inflammation. Increased levels of tumor markers are also associated with pregnancy.
Variations in levels are even more prominent in pregnancies complicated by obstetric
issues [21]. For example, alfa-fetoprotein (AFP) is a marker for hepatocellular carcinoma
and is elevated in the maternal circulation by fetal production, and this level may be up to
13 times higher in pregnancy complications such as preeclampsia [22]. Similarly, levels of
CA-125 may be elevated in pregnancy, especially in the first trimester [23]. During breast
cancer and pregnancy, carbohydrate antigen 15-3 (CA 15-3) levels significantly increase,
especially in the third trimester, showing a 3.3–20.0% increase above cut-off levels [21,24].
There are, however, traditional tumor markers that seem to be unaffected in pregnancy,
including lactate dehydrogenase (LDH), Inhibin-B, anti-Mullerian hormone (AMH), carcino-
embryonic antigen (CEA), CA-19-9, and human epididymis protein 4(HE4) [25–27].
The utilization of single-day protocols for sentinel node procedures during pregnancy
is generally regarded as a safe and well-tolerated approach [28]. When administered at
low doses that do not exceed a fetal exposure of 5 mGy, radiopharmaceuticals can be
effectively employed for these procedures, offering a viable and safe method that ensures
both maternal and fetal well-being [29].

5. Treatment Considerations
5.1. Multidisciplinary Approach in Managing Cancer during Pregnancy
The diagnosis of cancer during pregnancy is an extremely sensitive situation, requiring
delicate and specialized care by a multidisciplinary team. It is also important that such
cases are managed at a higher-level care center, with the access to resources and specialists
necessary to address all aspects of treatment [2]. It is important for a maternal fetal medicine
specialist and the relevant oncology specialists, along with the primary care provider and
an appropriate mental health professional, if required, to be involved. This constitutes
high-value care covering all aspects of the mother’s and fetus’ well-being.
A recent article by Silverstein et al., the authors suggest counseling patients about
pregnancy termination when appropriate for the kind of cancer and the gestational age
at diagnosis, especially in cases of an aggressive or advanced stage of cancer being found
early in pregnancy [30]. However, according to Wolters et al., no studies have shown an
improved maternal prognosis, as very few case control studies exist on this topic [28]. They
recommend against the termination of pregnancy solely for the purpose of improving
maternal outcomes.

5.2. Chemotherapy
Chemotherapy is generally avoided during the first trimester as this may lead to
significant morbidity, especially congenital malformations [31–33]. A recent cohort study
found that the major congenital malformation rate among offspring was as high as 21.7%
(95% CI 7.5–43.7%) when associated with maternal exposure to chemotherapy prior to
12 weeks, compared with 3% in women who received chemotherapy after 12 weeks (95%
CI, 3.13–27.30) [34]. The nature and mechanisms by which chemotherapy induces these
malformations is not clearly understood and involves a variety of factors, including genetic
susceptibility, the timing of exposure to chemotherapy and the type of drug used [34]
Curr. Oncol. 2023, 30 9451

Defects in the eyes, genitalia, and central nervous system become obvious after birth and
develop throughout infancy and childhood [34,35].
As previously mentioned, in cases of advanced or aggressive cancers, counseling
patients regarding the termination of pregnancy is appropriate. Chemotherapy is generally
avoided during the first trimester of pregnancy to avoid interference with organogenesis.
There is a strict association between the initiation of chemotherapy and congenital malfor-
mations in the first trimester, namely defects in the heart, limbs, neural tube, palate, eyes
and ears [36,37]. The risk of malformations is reduced after this period and the incidence
is similar to the general population, without cancer and not receiving chemotherapy [38].
Drug passage through the placenta depends on factors like protein binding, lipid solubility,
and ionization constant. Fetal exposure to drugs is influenced by maternal pharmacoki-
netics, such as the volume of distribution, placental metabolism and excretion rate, pH
difference between maternal and fetal fluids, and hemodynamic changes during pregnancy.
Although several chemotherapeutic agents have a low molecular weight, are lipid-soluble
and are non-ionized, which are all factors that favor passive diffusion, concentrations of
these drugs are found to be significantly lower than in the maternal circulation. The admin-
istration of most cytotoxic drugs is considered relatively safe after the first trimester [38,39]
After reaching the 35-week gestational mark, the medical consensus typically leans
toward avoiding chemotherapy. This precautionary measure is taken to allow for a substan-
tial duration for the maternal and fetal bone marrow to recuperate adequately following the
conclusion of the last chemotherapy cycle, thereby optimizing the health and well-being of
both the expectant mother and the developing fetus in the lead-up to delivery [28]. Breast
feeding should be avoided in patients receiving chemotherapy [40].

5.3. Immunotherapy and Targeted Agents

The advent of immunotherapy in treating cancer in non-pregnant patients over the
years has fostered great research, in the form of clinical trials, but studies on the use of
these agents in pregnancy is limited.
During pregnancy, the maternal immune system faces the task of tolerating the fetus
while also protecting against infections and toxins. This process happens in three phases:
first, a pro-inflammatory state supports implantation and placenta formation; second,
an anti-inflammatory environment develops in the uterus during the second and third
trimesters; finally, a second pro-inflammatory stage triggers uterine contractions, fetal
delivery, and placental expulsion during parturition [41]. In the realm of immunotherapy,
immune checkpoint inhibitors (ICIs) stand out as the prevailing class of therapeutic agents.
This category encompasses inhibitors targeting programmed cell death protein 1 (PD-1),
programmed cell death ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4),
which are widely recognized and employed in clinical practice. Among the various other
agents utilized in this context, there are several noteworthy ones, such as certain cytokines,
primarily interferon alpha (IFNα) and interleukin-2 (IL-2). Additionally, the use of vaccines,
such as Bacillus Calmette–Guérin (BCG), and genetically engineered type 1 herpes simplex
viruses, along with specific T-cell engagers, have also been explored as potential therapeutic
approaches [42].
Current guidelines advise against ICI use in patients of childbearing age (unless
using effective contraception) during and for at least 5 months after the last dose of ICI
treatment [43]. A recent study sought to characterize the safety profile of ICIs in pregnancy
using the World Health Organization’s (WHO’s) spontaneous reporting system by way
of a disproportionality study. In this study, a total of 56 patients reported pregnancy-
related outcomes. The most common reported maternal outcomes were diarrhea (5.4%),
nausea, fatigue, abdominal pain, pruritis and chest pain (3.6%). The most common fetal
outcomes included spontaneous abortions (21.4%) and prematurity (32.1%). Uncomplicated
deliveries occurred in 7.1% of cases [44]. With regards to other immunotherapeutic agents,
there are limited data on the safety profile in terms of risks to the neonate.
Curr. Oncol. 2023, 30 9452

An analysis of clinical trials by Mittra et al. showed that, in a 10-year period from 2011
to 2020, seven patients who had a diagnosis of cancer during pregnancy and who decided
to take their pregnancy to term decided to continue treatment with immunotherapeutic
agents. All pregnancies resulted in vaginal births of apparently normal infants [45].

5.4. Surgical Interventions and Potential Effects on the Fetus

Surgery is generally not a contraindication regardless of gestational age. For gyne-
cological malignancies, it is preferably performed in the early second trimester when the
risk of miscarriage is lower and uterine size allows access [14]. For oncologic procedures,
the left lateral tilt position is advised due to the operating time and general anesthesia use,
while the right lateral tilt can be considered if it improves exposure [46]. The feasibility
of laparoscopy during pregnancy varies based on gestational age, surgeon’s experience,
procedure type, and the organs involved. A study comparing laparotomy to laparoscopy in
pregnant women revealed that laparoscopy resulted in fewer fetal adverse effects, shorter
operative times, and reduced hospital stays [47].

6. Ethical and Legal Perspectives

In a historic ruling on 22 January 1973, the United States Supreme Court ruled in favor
of a woman’s right to have an abortion. This meant that the decision on whether or not to
have an abortion fell within the realm of individual authority and not government authority.
This established the Fourteenth Amendment’s “liberty” guarantee, safeguarding personal
privacy, encompassing the right to abortion before fetal viability. Since then, the Supreme
Court has consistently upheld this constitutional protection for abortion as a fundamental
aspect of liberty, interconnected with the ability to make personal choices concerning family,
relationships, and bodily autonomy. However, on 24 June 2022, this landmark ruling
was overturned, ending national protection to this constitutional right [48]. There were
approximately 3.6 million live births in the United States in 2022, and a total of 21 states have
now either completely banned or imposed restrictions on abortion at the time of writing this
article. This means that approximately 40% of live births occurred in states where abortion
is restricted or banned. At least 1500 individuals will develop pregnancy-associated cancer
in these states. Between 135 and 420 individuals with pregnancy-associated cancer will
receive suboptimal care and may face mortality because an abortion needed to start therapy
may not be protected by law [49].
The embryo or fetus’s age significantly impacts access to pregnancy termination as
governed by evolving state laws. Medical viability begins around 24 weeks, with a high risk
of severe prematurity until 28 weeks, linked to neonatal issues. Even though late-preterm
complications are rare (34–36 weeks), experts suggest supporting the fetus until 37 weeks
for better outcomes [30,50]. When a viable yet preterm fetus conflicts with the safety
of the mother’s therapy, balancing the risks of early delivery against delayed oncologic
treatment becomes crucial. Complex medical choices are frequently swayed by religious,
cultural, and personal beliefs, alongside factors like family dynamics, community influence,
and trust in healthcare providers. Notably, some religions and cultures oppose ending
pregnancies, even if it endangers the mother’s life. In instances where a mother receives a
terminal diagnosis, the idea of raising a child without her and the financial burden can be
inconceivable. Additionally, a first-time mother’s decisions about her survival versus the
fetus may contrast with those of a mother already caring for dependents.
Pregnancy termination constraints will mainly impact cases where urgent oncologic
therapy is required, yet contradicted due to pregnancy, and the fetus is not viable. Decisions
about emergency terminations or when life is at risk hinge on specific state regulations. Acts
like the Emergency Medical Treatment & Labor Act (EMTALA) guarantee emergency care to
all patients, irrespective of their financial status [51,52]. Recent federal guidance reaffirmed
that abortion is allowed in cases of medical emergencies, such as ectopic pregnancy or severe
preeclampsia, regardless of state regulations [53]. While cancer can be life-threatening, it
Curr. Oncol. 2023, 30 9453

is uncertain if it qualifies as an emergency warranting immediate treatment under these

provisions.
Lawmakers refer to the “constitutional right to interstate travel” as an option to
seek abortion in another state, but ongoing debates continue [54]. This safeguard may
only benefit those with the means to travel, disproportionately impacting disadvantaged
patients. Oncologists practicing in states with abortion restrictions will face challenges in
advising terminations based on medical reasons.

7. Maternal and Fetal Outcomes

7.1. Maternal Prognosis and Long-Term Effects of Cancer Treatment
Maternal outcomes may be cancer-specific. In general, there is not much difference
in cause-specific deaths between pregnant or lactating women compared to non-pregnant
women with cancer, as seen in a cohort study conducted by Stensheim et al. [55]. In
this study of 42,511 women who were diagnosed with cancer during pregnancy between
1967 and 2002, outcomes were monitored over a median period of 9 years. They were
grouped as non-pregnant, pregnant or lactating at diagnosis. Across all sites, there were no
significant differences in cause-specific death rates between groups. Within the pregnant
group, the HR stood at 1.03, accompanied by a 95% confidence interval (CI) ranging from
0.86 to 1.22. Conversely, the lactating group displayed a marginally lower HR of 1.02,
with a corresponding 95% CI of from 0.86 to 1.22. A specific subset of patients diagnosed
with breast cancer demonstrated a substantially higher HR of 1.95. This increased risk
of cause-specific death was statistically significant, as evidenced by the 95% CI ranging
from 1.36 to 2.78. Similarly, for patients diagnosed with ovarian cancer during lactation,
the HR climbed to 2.23, again with a notable 95% CI, this time spanning from 1.05 to 4.73.
These observations underscore the critical impact of timing, specifically lactation, on the
prognosis for patients facing these particular cancer types, warranting focused attention
and further investigation into the underlying factors contributing to this elevated risk.
A slight increase in this risk was observed for malignant melanoma diagnosed during
pregnancy. Interestingly, women with post-cancer pregnancies experienced a significant
decrease in the risk of cause-specific death across all cancer types [55].
Within the realm of breast cancer research, a meta-analysis, led by Hartman et al. [56],
assessed overall survival (OS) and disease-free survival (DFS) among a diverse cohort. This
cohort consisted of patients diagnosed with breast cancer either during their pregnancy or
up to five years after childbirth. The subanalysis of these data brought to light co insights
into the varied survival outcomes within these subgroups. The subgroup encompassing
patients diagnosed with breast cancer during pregnancy or postpartum (PABC) demon-
strated a distinct, less favorable trend in overall survival (OS). The hazard ratio (HR) for
this particular subgroup was estimated at 1.46, as substantiated by the 95% confidence
interval (CI) ranging from 1.17 to 1.82. This marked an increased risk of adverse outcomes.
Furthermore, the investigation singled out patients diagnosed with breast cancer during
pregnancy alone, with the results indicating a similarly heightened risk of compromised
OS. The HR in this context was found to be 1.47, and the 95% CI spanned from 1.04 to
2.08, when compared to non-pregnant women of the same age. Similar results were seen in
DFS among patients with pregnancy-associated breast cancer (HR 1.51; 95% CI 1.22–1.88).
Pregnant women diagnosed with malignant melanoma exhibited a heightened risk of
cause-specific death (HR 1.52). However, cervical, thyroid, and ovarian cancer, as well as
lymphoma or leukemia, did not exhibit significantly altered cause-specific death risks (HR
1.23, HR 0.89, HR 1.15, HR 4.58, and HR 0.46, respectively) [56].
In another study, patients diagnosed with pregnancy during cancer and in the first-
year post-partum were found to be in more advanced stages of the disease compared
to non-pregnant patients. Additionally, for all cancer types, patients with pregnancy-
associated cancer had a similar overall survival with a hazard ratio (HR) of 1.07 (95% CI
0.80–1.41) for the pregnancy group and HR 1.02 (95% CI 0.88–1.18) for the postpartum
group [57] In general, maternal outcomes seem to depend on the type of cancer and the
Curr. Oncol. 2023, 30 9454

stage at which they are diagnosed but, when combined, outcomes appear to be similar to
non-pregnant patients.

7.2. Fetal Outcomes

A multicenter case-control study conducted by Amant et al. [58] studied fetal outcomes
in mothers who received chemotherapy, radiation, and had surgery during pregnancy.
Throughout pregnancy, chemotherapy, either as a sole treatment or in combination
with other therapies, was administered to 74% of children, while 8.5% received radiotherapy,
either as a standalone treatment or in combination. A further 10.1% underwent surgery as
their exclusive therapeutic intervention, 1.6% were treated with alternative drug therapies,
and 10.9% received no treatment. It is noteworthy that, in the prenatal-exposure group,
22.0% of infants exhibited birth weights below the 10th percentile, in contrast to 15.2%
in the control group, although this difference was not statistically significant (p = 0.16).
Furthermore, cognitive development did not display any notable variation between the
two groups. Moreover, a cardiologic evaluation conducted on 47 children at 36 months of
age revealed that cardiac findings remained within the normal range [58].
In another multicenter cohort study examining outcomes at 6 years post-partum with
a sample of 132 children, statistically significant differences were found in mean verbal
Intelligence Quotient (IQ) and visuospatial long-term memory. Additionally, a significant
difference in diastolic blood pressure was found, with higher values in the chemotherapy-
exposed group. Additionally, ototoxicity was found in 3 cases of exposure to cisplatin.
There were, however, no differences in overall IQ [59].
Cardonick et al. reported that the majority of children exposed to chemotherapy did
not show any significant complications [35]. A study led by Murthy et al. indicates that
administering 5-fluorouracil, doxorubicin, and cyclophosphamide to pregnant women
with breast cancer during the second and third trimesters is a safe therapeutic option.
This treatment approach does not appear to raise significant concerns regarding severe
complications or immediate health risks for offspring exposed to chemotherapy in utero [60].
Another study found that the incidence of birth defects of infants followed up to 7 years
was the same as the CDC-reported national average of 3% [61].
It is necessary to monitor newborns very closely to observe for side effects and the
assessment must be made on a case-by-case basis depending on the type of cancer and
type of treatment. Wolters et al. [28] recommend baseline screening with a neonatal
complete blood count (CBC), especially if the last chemotherapy was within three weeks
of delivery. Screening for cardiac abnormalities should be carried out in instances of
anthracycline exposure with an echocardiogram during the neonatal period. Children who
have been exposed to platinum-based chemotherapy should undergo screening for auditory
impairment using otoacoustic emissions until they reach the age of 5, after which regular
audiometry tests should be conducted at subsequent stages of development. Additionally,
if placental metastases are suspected, a liver function test and abdominal ultrasound should
be carried out. Close attention must be paid to developmental milestones in consultation
with a pediatrician.

8. Preservation of Fertility
For many women, having children after being diagnosed with cancer is a key compo-
nent of psychological well-being. Experiencing infertility on its own is linked to consider-
able psychological distress, resulting in depression rates twice as high as those found in the
general population [62]. Additionally, this leads to a reduction in the quality of life concern-
ing emotional well-being, relationships, and sexuality. A study by Schover et al. showed
that 76% of cancer patients of child-bearing age wished to have children after recovering
from cancer [63]. The risk of infertility with cancer treatment is mostly dependent on the
patient’s age and the type of treatment received. Most fertility preservation techniques for
women, such as embryo cryopreservation, oocyte preservation, ovarian tissue preservation,
ovarian transposition and hormonal treatment, are not viable for use during pregnancy [64].
Curr. Oncol. 2023, 30 9455

It is, therefore, prudent to offer these options following delivery, along with an evaluation
of reproductive capacity.

9. Conclusions
A diagnosis of cancer during pregnancy adds to the many challenges that patients
already face regarding the pregnancy itself. It is additionally challenging to all provider
teams involved, and in the wake of the recent overturning of abortion laws it is important
to have clarity and clear guidelines on how best to approach a situation that is already
medically complex. Various tumor markers behave differently throughout the course of
pregnancy. Chemotherapy and targeted therapies are generally avoided during the first
trimester, but studies show that they are safe later during the pregnancy. Radiation is
avoided throughout pregnancy. Maternal outcomes are generally favorable following
delivery, but more studies are required to assess long-term fetal outcomes and side effects.

Author Contributions: G.A.: methodology, investigation, writing—original draft, writing—review

and editing; N.S.: conceptualization, methodology, supervision. All authors have read and agreed to
the published version of the manuscript.
Funding: This research received no external funding.
Conflicts of Interest: The authors have no conflict of interest to declare.

References
1. Pavlidis, N.A. Coexistence of pregnancy and malignancy. Oncologist 2002, 7, 279–287. [CrossRef] [PubMed]
2. Schwab, R.; Anic, K.; Hasenburg, A. Cancer and Pregnancy: A Comprehensive Review. Cancers 2021, 13, 3048. [CrossRef]
[PubMed]
3. Matsuo, K.; Klar, M.; Youssefzadeh, A.C.; Mandelbaum, R.S.; Roman, L.D.; Ouzounian, J.G.; Wright, J.D. Assessment of Severe
Maternal Morbidity and Mortality in Pregnancies Complicated by Cancer in the US. JAMA Oncol. 2022, 8, 1213–1216. [CrossRef]
[PubMed]
4. PDQ Adult Treatment Editorial Board. Breast Cancer Treatment During Pregnancy (PDQ® ): Health Professional Version. PDQ
Cancer Information Summaries. 2002. Available online: https://www.cancer.gov/types/breast/hp/pregnancy-breast-treatmen
t-pdq (accessed on 22 September 2023).
5. Al-Halal, H.; Kezouh, A.; Abenhaim, H.A. Incidence and obstetrical outcomes of cervical intraepithelial neoplasia and cervical
cancer in pregnancy. Arch. Gynecol. Obstet. 2012, 287, 245–250. [CrossRef]
6. De Vincenzo, R.; Tortorella, L.; Ricci, C.; Cavaliere, A.F.; Zannoni, G.F.; Cefalo, M.G.; Scambia, G.; Fagotti, A. Locally advanced
cervical cancer complicating pregnancy: A case of competing risks from the Catholic University of the Sacred Heart in Rome.
Gynecol. Oncol. 2018, 150, 398–405. [CrossRef]
7. Dunleavy, K.; McLintock, C. How I treat lymphoma in pregnancy. Blood 2020, 136, 2118–2124. [CrossRef]
8. Zhu, D.; Tang, D.; Chai, X.; Zhang, G.; Wang, Y. Acute leukemia in pregnancy: A single institutional experience with 21 cases at
10 years and a review of the literature. Ann. Med. 2021, 53, 567–575. [CrossRef]
9. Kwon, Y.-S.; Mok, J.-E.; Lim, K.-T.; Lee, I.-H.; Kim, T.-J.; Lee, K.-H.; Shim, J.-U. Ovarian Cancer during Pregnancy: Clinical and
Pregnancy Outcome. J. Korean Med. Sci. 2010, 25, 230–234. [CrossRef]
10. Wielowieyska-Szybińska, D.K.; Spałkowska, M.; Wojas-Pelc, A. Melanoma in pregnancy: A case report and review of the
literature. Postep. Derm. Alergol. 2015, 6, 483–487. [CrossRef]
11. Khaled, H.; Al Lahloubi, N.; Rashad, N. A review on thyroid cancer during pregnancy: Multitasking is required. J. Adv. Res. 2016,
7, 565–570. [CrossRef]
12. Yang, H.; Han, X. Colorectal cancer in pregnancy: A case report and literature review. J. Gastrointest. Oncol. 2021, 12, 885–891.
[CrossRef]
13. Lee, Y.; Roberts, C.; Dobbins, T.; Stavrou, E.; Black, K.; Morris, J.; Young, J. Incidence and outcomes of pregnancy-associated
cancer in Australia, 1994–2008: A population-based linkage study. BJOG Int. J. Obstet. Gynaecol. 2012, 119, 1572–1582. [CrossRef]
14. Han, S.N.; Lotgerink, A.; Gziri, M.M.; Van Calsteren, K.; Hanssens, M.; Amant, F. Physiologic variations of serum tumor markers
in gynecological malignancies during pregnancy: A systematic review. BMC Med. 2012, 10, 86. [CrossRef] [PubMed]
15. Yaghoobi, M.; Koren, G.; Nulman, I. Challenges to diagnosing colorectal cancer during pregnancy. Can. Fam. Physician. 2009, 55,
881–885. [PubMed]
16. Hepner, A.; Negrini, D.; Hase, E.A.; Exman, P.; Testa, L.; Trinconi, A.F.; Filassi, J.R.; Francisco, R.P.V.; Zugaib, M.;
O’connor, T.L.; et al. Cancer During Pregnancy: The Oncologist Overview. World J. Oncol. 2019, 10, 28–34. [CrossRef]
[PubMed]
17. Vandecaveye, V.; Amant, F.; Lecouvet, F.; Van Calsteren, K.; Dresen, R.C. Imaging modalities in pregnant cancer patients. Int. J.
Gynecol. Cancer 2021, 31, 423–431. [CrossRef] [PubMed]
Curr. Oncol. 2023, 30 9456

18. Jha, P.; Pōder, L.; Glanc, P.; Patel-Lippmann, K.; McGettigan, M.; Moshiri, M.; Nougaret, S.; Revzin, M.V.; Javitt, M.C. Imaging
Cancer in Pregnancy. RadioGraphics 2022, 42, 1494–1513. [CrossRef]
19. Zanotti-Fregonara, P.; Ishiguro, T.; Yoshihara, K.; Ishii, S.; Enomoto, T. 18 F-FDG Fetal Dosimetry Calculated with PET/MRI.
J. Nucl. Med. 2022, 63, 1592–1597. [CrossRef]
20. Ishiguro, T.; Nishikawa, N.; Ishii, S.; Yoshihara, K.; Haino, K.; Yamaguchi, M.; Adachi, S.; Watanabe, T.; Soeda, S.; Enomoto, T.
PET/MR imaging for the evaluation of cervical cancer during pregnancy. BMC Pregnancy Childbirth 2021, 21, 288. [CrossRef]
21. Han, S.N.; Amant, F.; Cardonick, E.H.; Loibl, S.; Peccatori, F.A.; Gheysens, O.; Sangalli, C.A.; Nekljudova, V.; Steffensen, K.D.;
Gziri, M.M.; et al. Axillary staging for breast cancer during pregnancy: Feasibility and safety of sentinel lymph node biopsy.
Breast Cancer Res. Treat. 2017, 168, 551–557. [CrossRef]
22. Sarandakou, A.; Protonotariou, E.; Rizos, D. Tumor Markers In Biological Fluids Associated With Pregnancy. Crit. Rev. Clin. Lab.
Sci. 2007, 44, 151–178. [CrossRef] [PubMed]
23. Amampai, R.; Suprasert, P. Cancer Antigen 125 during Pregnancy in Women without Ovarian Tumor Is Not Often Rising. Obstet.
Gynecol. Int. 2018, 2018, 8141583. [CrossRef] [PubMed]
24. Buonomo, B.; A Noli, S.; Santini, A.; Alviggi, C.; A Peccatori, F. Can we trust tumour markers in pregnancy after breast cancer? A
case of elevated CA 15-3 in the third trimester of pregnancy normalising after delivery. ecancer 2019, 13, 979. [CrossRef] [PubMed]
25. Makkonen, M.; Penttilä, I.M.; Castrén, O. Serum Lactic Acid Dehydrogenase and Isoenzymes During Pregnancy and Labor. Acta
Obstet. et Gynecol. Scand. 1980, 59, 97–101. [CrossRef]
26. Ercan, Ş.; Kaymaz, Ö.; Yücel, N.; Orçun, A. Serum concentrations of CA 125, CA 15-3, CA 19-9 and CEA in normal pregnancy: A
longitudinal study. Arch. Gynecol. Obstet. 2011, 285, 579–584. [CrossRef] [PubMed]
27. La Marca, A.; Giulini, S.; Orvieto, R.; De Leo, V.; Volpe, A. Anti-Müllerian hormone concentrations in maternal serum during
pregnancy. Hum. Reprod. 2005, 20, 1569–1572. [CrossRef]
28. Wolters, V.; Heimovaara, J.; Maggen, C.; Cardonick, E.; Boere, I.; Lenaerts, L.; Amant, F. Management of pregnancy in women
with cancer. Int. J. Gynecol. Cancer 2021, 31, 314–322. [CrossRef]
29. Mitchell, K.B.; Fleming, M.M.; Anderson, P.O.; Giesbrandt, J.G.; Young, M.; Noble, L.; Reece-Stremtan, S.; Bartick, M.; Calhoun, S.;
Dodd, S.; et al. ABM Clinical Protocol #31: Radiology and Nuclear Medicine Studies in Lactating Women. Breastfeed. Med. 2019,
14, 290–294. [CrossRef]
30. Silverstein, J.; Post, A.L.; Chien, A.J.; Olin, R.; Tsai, K.K.; Ngo, Z.; Van Loon, K. Multidisciplinary Management of Cancer During
Pregnancy. JCO Oncol. Pract. 2020, 16, 545–557. [CrossRef]
31. Wolters, V.; Amant, F. Chemotherapy During Pregnancy: Careful Fetal Growth Monitoring Is Mandatory. JCO Oncol. Pract. 2020,
16, 559–560. [CrossRef]
32. Lishner, M.; Avivi, I.; Apperley, J.F.; Dierickx, D.; Evens, A.M.; Fumagalli, M.; Nulman, I.; Oduncu, F.S.; Peccatori, F.A.;
Robinson, S.; et al. Hematologic Malignancies in Pregnancy: Management Guidelines From an International Consensus Meeting.
J. Clin. Oncol. 2016, 34, 501–508. [CrossRef] [PubMed]
33. Korakiti, A.-M.; Zografos, E.; Van Gerwen, M.; Amant, F.; Dimopoulos, M.-A.; Zagouri, F. Long-Term Neurodevelopmental
Outcome of Children after in Utero Exposure to Chemotherapy. Cancers 2020, 12, 3623. [CrossRef] [PubMed]
34. van Gerwen, M.; Maggen, C.; Cardonick, E.; Verwaaijen, E.J.; Heuvel-Eibrink, M.v.D.; Shmakov, R.G.; Boere, I.; Gziri, M.M.;
Ottevanger, P.B.; Lok, C.A.R.; et al. Association of Chemotherapy Timing in Pregnancy With Congenital Malformation. JAMA
Netw. Open 2021, 4, e2113180. [CrossRef] [PubMed]
35. Cardonick, E.; Iacobucci, A. Use of chemotherapy during human pregnancy. Lancet Oncol. 2004, 5, 283–291. [CrossRef] [PubMed]
36. de Haan, J.; Verheecke, M.; Van Calsteren, K.; Van Calster, B.; Shmakov, R.G.; Gziri, M.M.; Halaska, M.J.; Fruscio, R.; Lok, C.A.R.;
A Boere, I.; et al. Oncological management and obstetric and neonatal outcomes for women diagnosed with cancer during
pregnancy: A 20-year international cohort study of 1170 patients. Lancet Oncol. 2018, 19, 337–346. [CrossRef]
37. Al-Jebari, Y.; Glimelius, I.; Nord, C.B.; Cohn-Cedermark, G.; Ståhl, O.; Tandstad, T.; Jensen, A.; Haugnes, H.S.; Daugaard, G.;
Rylander, L.; et al. Cancer therapy and risk of congenital malformations in children fathered by men treated for testicular
germ-cell cancer: A nationwide register study. PLOS Med. 2019, 16, e1002816. [CrossRef]
38. Esposito, S.; Tenconi, R.; Preti, V.; Groppali, E.; Principi, N. Chemotherapy against cancer during pregnancy. Medicine 2016, 95,
e4899. [CrossRef]
39. Feghali, M.; Venkataramanan, R.; Caritis, S. Pharmacokinetics of drugs in pregnancy. Semin. Perinatol. 2015, 39, 512–519.
[CrossRef]
40. Sorosky, J.I.; Sood, A.K.; Buekers, T.E. THE USE OF CHEMOTHERAPEUTIC AGENTS DURING PREGNANCY. Obstet. Gynecol.
Clin. N. Am. 1997, 24, 591–599. [CrossRef]
41. Koutras, A.; Ntounis, T.; Fasoulakis, Z.; Papalios, T.; Pittokopitou, S.; Prokopakis, I.; Syllaios, A.; Valsamaki, A.; Chionis, A.;
Symeonidis, P.; et al. Cancer Treatment and Immunotherapy during Pregnancy. Pharmaceutics 2022, 14, 2080. [CrossRef]
42. Brahmer, J.R.; Abu-Sbeih, H.; Ascierto, P.A.; Brufsky, J.; Cappelli, L.C.; Cortazar, F.B.; E Gerber, D.; Hamad, L.; Hansen, E.;
Johnson, D.B.; et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-
related adverse events. J. Immunother. Cancer 2021, 9, e002435. [CrossRef] [PubMed]
43. Borgers, J.S.W.; Heimovaara, J.H.; Cardonick, E.; Dierickx, D.; Lambertini, M.; Haanen, J.B.A.G.; Amant, F. Immunotherapy for
cancer treatment during pregnancy. Lancet Oncol. 2021, 22, e550–e561. [CrossRef] [PubMed]
Curr. Oncol. 2023, 30 9457

44. Noseda, R.; Müller, L.; Bedussi, F.; Fusaroli, M.; Raschi, E.; Ceschi, A. Immune Checkpoint Inhibitors and Pregnancy: Analysis of
the VigiBase® Spontaneous Reporting System. Cancers 2022, 15, 173. [CrossRef] [PubMed]
45. Mittra, A.; Naqash, A.R.; Murray, J.H.; Finnigan, S.; Kwak-Kim, J.; Ivy, S.P.; Chen, A.P.; Sharon, E. Outcomes of Pregnancy During
Immunotherapy Treatment for Cancer: Analysis of Clinical Trials Sponsored by the National Cancer Institute. Oncologist 2021, 26,
e1883–e1886. [CrossRef]
46. Pearl, J.; Price, R.; Richardson, W.; Fanelli, R. Guidelines for diagnosis, treatment, and use of laparoscopy for surgical problems
during pregnancy. Surg. Endosc. 2011, 25, 3479–3492. [CrossRef]
47. Shigemi, D.; Aso, S.; Matsui, H.; Fushimi, K.; Yasunaga, H. Safety of Laparoscopic Surgery for Benign Diseases during Pregnancy:
A Nationwide Retrospective Cohort Study. J. Minim. Invasive Gynecol. 2018, 26, 501–506. [CrossRef]
48. Lazzarini, Z. The End of Roe v. Wade—States’ Power over Health and Well-Being. New Engl. J. Med. 2022, 387, 390–393. [CrossRef]
49. Suran, M. Treating Cancer in Pregnant Patients After Roe v Wade Overturned. JAMA 2022, 328, 1674–1676. [CrossRef]
50. Fanczal, E.; Berecz, B.; Szijártó, A.; Gasparics, Á.; Varga, P. The Prognosis of Preterm Infants Born at the Threshold of Viability:
Fog Over the Gray Zone—Population-Based Studies of Extremely Preterm Infants. Experiment 2020, 26, e926947-1–e926947-12.
[CrossRef] [PubMed]
51. Zibulewsky, J. The Emergency Medical Treatment and Active Labor Act (Emtala): What It Is and What It Means for Physicians.
Proceedings 2001, 14, 339–346. [CrossRef]
52. CMS. Reinforcement of EMTALA Obligations Specific to Patients Who Are Pregnant or Are Experiencing Pregnancy Loss
(UPDATED JULY 2022). Available online: https://www.cms.gov/medicareprovider-enrollment-and-certificationsurveycertificat
iongeninfopolicy-and-memos-states-and/reinforcement-emtala-obligations-specific-patients-who-are-pregnant-or-are-experi
encing-pregnancy-0 (accessed on 22 September 2023).
53. Suran, M. Federal Guidance Clarifies Abortion as Emergency Care. JAMA 2022, 328, 699. [CrossRef] [PubMed]
54. Parfomak, P.W. Pipeline Transportation of Hydrogen: Regulation, Research, and Policy. Congressional Research Service (CRS).
CRS Report R46700. Available online: https://crsreports.congress.gov (accessed on 2 March 2021).
55. Stensheim, H.; Møller, B.; van Dijk, T.; Fosså, S.D. Cause-Specific Survival for Women Diagnosed With Cancer During Pregnancy
or Lactation: A Registry-Based Cohort Study. J. Clin. Oncol. 2009, 27, 45–51. [CrossRef] [PubMed]
56. Hartman, E.K.; Eslick, G.D. The prognosis of women diagnosed with breast cancer before, during and after pregnancy: A
meta-analysis. Breast Cancer Res. Treat. 2016, 160, 347–360. [CrossRef] [PubMed]
57. Li, S.; Hsu, Y.; Yen, C.; Chen, Y.; Wu, P.; Chang, K.; Li, C.; Chen, T. Maternal survival of patients with pregnancy-associated
cancers in Taiwan—A national population-based study. Cancer Med. 2020, 9, 9431–9444. [CrossRef] [PubMed]
58. Amant, F.; Vandenbroucke, T.; Verheecke, M.; Fumagalli, M.; Halaska, M.J.; Boere, I.; Han, S.; Gziri, M.M.; Peccatori, F.;
Rob, L.; et al. Pediatric Outcome after Maternal Cancer Diagnosed during Pregnancy. New Engl. J. Med. 2015, 373, 1824–1834.
[CrossRef]
59. Vandenbroucke, T.; Verheecke, M.; van Gerwen, M.; Van Calsteren, K.; Halaska, M.J.; Fumagalli, M.; Fruscio, R.; Gandhi, A.;
Veening, M.; Lagae, L.; et al. Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy. Eur.
J. Cancer 2020, 138, 57–67. [CrossRef]
60. Murthy, R.K.; Theriault, R.L.; Barnett, C.M.; Hodge, S.; Ramirez, M.M.; Milbourne, A.; A Rimes, S.; Hortobagyi, G.N.; Valero, V.;
Litton, J.K. Outcomes of children exposed in uteroto chemotherapy for breast cancer. Breast Cancer Res. 2014, 16, 500. [CrossRef]
61. Mai, C.T.; Isenburg, J.L.; Canfield, M.A.; Meyer, R.E.; Correa, A.; Alverson, C.J.; Lupo, P.J.; Riehle-Colarusso, T.; Cho, S.J.;
Aggarwal, D.; et al. National population-based estimates for major birth defects, 2010–2014. Birth Defects Res. 2019, 111, 1420–1435.
[CrossRef]
62. Carter, J.; Rowland, K.; Chi, D.; Brown, C.; Abu-Rustum, N.; Castiel, M.; Barakat, R. Gynecologic cancer treatment and the impact
of cancer-related infertility. Gynecol. Oncol. 2005, 97, 90–95. [CrossRef]
63. Schover, L.R.; Rybicki, L.A.; Martin, B.A.; Bringelsen, K.A. Having children after cancer. Cancer 1999, 86, 697–709. [CrossRef]
64. Duffy, C.; Allen, S. Medical and Psychosocial Aspects of Fertility After Cancer. Cancer J. 2009, 15, 27–33. [CrossRef] [PubMed]

Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual
author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to
people or property resulting from any ideas, methods, instructions or products referred to in the content.