First Reported Case of Successful Conception and Delivery During Stage IV Breast Cancer Treatment

Breast cancer is the most common cancer in women and is especially concerning because it is the leading cause of cancer-related deaths in women under 40.^2,3 Among different types of breast cancer, there’s one called pregnancy-associated breast cancer, which can occur during pregnancy, in the first year after childbirth, or while a woman is breastfeeding.⁴ The number of pregnancy-associated breast cancer cases is increasing, largely due to the trend of women delaying pregnancy. This type of breast cancer is relatively rare, occurring in 3 out of 1,000 pregnancies, but is particularly aggressive.² Diagnosis can be delayed because the physiological changes during pregnancy can make it harder to detect, and there is often a lack of awareness about it in the medical community.^2,3

Although there have been cases where advanced-stage cancer was diagnosed during pregnancy, our research has not discovered any prior instances of someone becoming pregnant while actively receiving treatment for stage IV cancer.^1,4

Case Presentation¹

• In September 2015, a 34-year-old woman was diagnosed with stage III invasive ductal breast cancer (ER-negative, PR-negative, HER-2-positive +3).
• She underwent mastectomy, lymph node dissection, and reconstruction at MD Anderson Cancer Center, followed by dose-dense doxorubicin and cyclophosphamide chemotherapy.
• She received Trastuzumab and paclitaxel for four cycles and then Trastuzumab alone.
• In June 2016, she developed cardiomyopathy, leading to Trastuzumab discontinuation. Monthly echocardiography showed stable, but no improved cardiac function, and Trastuzumab was paused for six months.
• Reconstructive surgery in March 2017 improved her ejection fraction (EF), allowing her to receive two more cycles of Trastuzumab.
• In October 2017, scans revealed lung and mediastinal lymph node metastases and genetic testing was negative for driver mutations.
• Her treatment was changed to ado-Trastuzumab Emtansine (TDM-1), which was stopped after 12 cycles due to fatigue and liver toxicity.
• She then received dual-antibody Trastuzumab-Pertuzumab starting in February 2018, with multiple interruptions due to EF drops below 40%.
• After an EF recovery to over 50%, she resumed Trastuzumab-Pertuzumab.
• A CT scan in April 2020 showed no evidence of disease.
• Despite non-compliance with treatment schedules due to personal and social circumstances, her last imaging in September 2022 showed no evidence of disease.

Pregnancy Against the Odds¹

Following her gynecologist’s recommendations for regular exchanges, the patient had an intrauterine device (IUD) during her treatment. Without consulting her oncology team, she removed the IUD to become pregnant:

• In December 2022, just 12 days after her last treatment cycle, she sought an emergency consultation due to a positive home pregnancy test, indicating she had been pregnant for around ten weeks based on her previous menstrual period.
• Despite being advised to consider pregnancy termination because of recent exposure to anti-HER-2 agents (Trastuzumab-Pertuzumab), the patient was determined to continue the pregnancy, fully understanding that she would not receive further treatment during the remaining seven to eight months of pregnancy, which could affect her prognosis.
• She was aware of the risks of fetal malformations and potential negative outcomes for both her and the fetus. A referral to a clinical psychologist was offered but declined by the patient.
• After making an informed decision, the patient chose to discontinue all treatment and be monitored until delivery. She was closely monitored in the clinic.
• At Clinic, the patient had an extensive 11 to 14 week scan, including cell-free fetal DNA testing, to rule out common chromosomal abnormalities.
• Comprehensive counseling covered the risks of structural malformations and chromosomal abnormalities, with an estimated overall risk of 1% to 5%.
• Baseline tests included pulmonary function, electrocardiography, and ECHO to assess cardiac function.
• The patient, fully committed to her pregnancy, understood the risks, including potential cardiac deterioration and breast cancer recurrence.
• Subsequent scans at 16 and 20 weeks revealed no major or minor congenital malformations. Uterine artery Doppler at 20 weeks showed a low risk for preeclampsia and fetal growth issues.
• Growth scans at 26 weeks indicated normal fetal growth and amniotic fluid volume.
• Repeat pulmonary function and ECHO at 32 weeks were stable.
• The patient had a history of four previous vaginal deliveries, and a spontaneous rupture of membranes at 38 weeks led to labor and an automatic vaginal delivery, resulting in a healthy baby boy.
• The newborn’s APGAR scores at 5 and 10 minutes were 9 and 10, respectively, indicating normal well-being. A list of recommended tests for monitoring during pregnancy is listed in Table 1.

^{Table 1: Recommended cardiac tests for monitoring during pregnancy.}

Three weeks after giving birth, she visited the oncology clinic for an evaluation. Her PET-CT scan showed no signs of abnormalities or metastatic disease, except for physiological findings in the left breast with no metastasis (Figure 1). Additionally, an ECHO was performed, revealing a normal ejection fraction (EF) of over 55%. A specialized neonatal cardiac assessment was also carried out, showing a normal evaluation of the infant (Figures 2-3).

^{Figure 1: In the sagittal PET-CT image taken postpartum, there is no indication of the disease, and only normal physiological uptake is observed in the left breast, without any signs of metastasis.
(Note: The acronym PET-CT stands for positron emission tomography-computed tomography.)}

^{Figure 2: The baby’s abdominal circumference, monitored throughout the pregnancy, consistently shows growth at the 50th percentile, which is indicative of normal development.}

^{Figure 3: The estimated fetal weight during the entire pregnancy suggests that the baby is experiencing normal growth, consistently aligning with the 50th percentile.}

The patient received counseling regarding the possibility of resuming treatment with either Trastuzumab-Pertuzumab or Trastuzumab alone. She decided to postpone any decisions for three months, expressing her intention to breastfeed her child (see Table 2).

^{Table 2: Chronological sequence of events.
*Pertuzumab was approved in the United States in December 2017.}

Discussion¹

Pregnancy while undergoing active systemic therapy for breast cancer is a complex and rare situation with potential risks. A case report details a unique scenario where a patient became pregnant while on active treatment with Trastuzumab and Pertuzumab.

Treatment with Trastuzumab during pregnancy can lead to severe complications for both the mother and the baby, such as oligohydramnios/anhydramnios. A review of multiple studies suggests that stopping Trastuzumab during pregnancy may be the safest action.^2,3

Trastuzumab with Pertuzumab can also cause complications during pregnancy, including fetal growth retardation and anhydramnios. Using effective contraception methods to prevent pregnancy while on these medications is highly recommended.³

In practice, it is strongly encouraged to use effective contraception, such as a copper IUD, for premenopausal women with cancer receiving systemic therapy to prevent complications and treatment interruption. When a woman becomes pregnant during cancer treatment, consulting with a medical oncologist and a maternal-fetal medicine specialist is essential to weigh the risks and benefits of continuing or stopping treatment.^2,3,4

In the case presented, the patient decided to delay her treatment decision for three months to continue breastfeeding her child. The optimal duration of Trastuzumab treatment in patients with no evidence of disease is not well-defined, and individual factors should be considered in these decisions.

Interrupting hormonal therapy in the adjuvant setting for early breast cancer has gained attention, particularly in select women attempting pregnancy. However, the feasibility and safety of pregnancy in stage IV breast cancer patients remain unclear due to limited data.

Despite the patient’s recurrent cardiac issues during anti-HER-2 therapy, her pregnancy did not result in complications. Her cardiac function returned to normal after delivery, consistent with the reversible dysfunction associated with anti-HER-2 therapy.

^{Table 3: Possible abnormalities associated with exposure to Trastuzumab and/or Pertuzumab in utero.
RDS, also known as respiratory distress syndrome}

Conclusion¹

This report presents a unique and previously unreported case in the medical literature. It involves a woman with metastatic breast cancer who became pregnant while actively receiving cancer treatment at our facility. This marks the first documented instance of a successful pregnancy and delivery in a patient with stage IV cancer while receiving active cancer treatment.

While this case had a positive outcome for both the mother and child, it’s essential to emphasize that we do not recommend such an approach for patients with advanced cancer due to the significant risks it poses to both the mother and the fetus. Managing such a complex scenario requires a multidisciplinary approach involving experienced oncologists, maternal-fetal specialists, and psychological support for the mother. Ensuring effective contraception during cancer treatment is vital to prevent such situations. Furthermore, additional research is needed to assess the long-term effects of anti-HER-2 therapies on children, as current studies have limited follow-up data.

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Reference

1. Al-Shamsi H O, Abdelwahed N, Singh M, et al. (October 17, 2023) First Reported Case of Successful Conception and Delivery During Stage IV Breast Cancer Treatment: A Case Report and Literature Review. Cureus 15(10): e47201. doi:10.7759/cureus.47201
2. Fazeli S, Sakala M, Rakow-Penner R, Ojeda-Fournier H: Cancer in pregnancy: breast cancer. Abdom Radiol (NY). 2023, 48:1645-62. 10.1007/s00261-023-03824-1
3. Annie Gives Birth with Stage-4 Colon Cancer. (2022). Accessed: October 2, 2023: https://www.saintjohnscancer.org/blog/annie-gives-birth-with-stage-4-colon-cancer/.
4. Al-Shamsi HO, Abdelwahed N, Al-Awadhi A, et al.: Breast cancer in the United Arab Emirates. JCO Glob Oncol. 2023, 9: e2200247. 10.1200/GO.22.00247
5. Hepner A., Negrini D., Hase E.A., et al.: Cancer during pregnancy: the oncologist overview. World J Oncol. 2019, 10:28-34. 10.14740%2Fwjon1177

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