Case reports
A Japanese mother was diagnosed with cervical squamous cell carcinoma three months postpartum, followed by radical hysterectomy and pelvic lymphadectomy immediately followed by four cycles of adjuvant chemotherapy, but the mother had a negative cervical cytology seven months before giving birth [1].
However, 23 months after her child was born, she went to the local hospital for 2 weeks of sputum production, and the CT showed multiple lumps spread along the bronchi in both lungs, and then a lung biopsy performed through visual thoracoscopic surgery (VATS) showed that neuroendocrine cancer had developed in the lungs.
Figure 1 Mother-to-child transmission of cancer Source network
Although the mother's diagnosed cervical squamous cell carcinoma and the child's diagnosis of neuroendocrine cancer were not a cancer, it was surprising that within 3 years of follow-up after the last treatment, the mother developed lung, liver and bone metastases. Histological examination of the mother's left lung tumor obtained by VATS shows hypodifferentiated carcinoma with neuroendocrine differentiation. Pathological review of hysterectomy specimens shows that cervical cancer is predominantly low-differentiated squamous cell carcinoma with focal neuroendocrine differentiation and a small amount of adenocarcinoma. Subsequently, genetic sequencing revealed that both the mother's and child's tumors were positive for human papillomavirus (HPV) type 18. Unfortunately, the mother passed away shortly after.
Another child went to a local hospital at the age of 6 with chest pain in his left side [1]. CT shows a lump with a diameter of 6 cm in the hilar area of the left lung, which is diagnosed with mucotic adenocarcinoma. Similar to the previous case, the child's mother was also detected for adenocarcinoma by cervical lesion biopsy after childbirth, and then genetic sequencing showed that both the mother's and the child's tumors were positive for HPV 16. The mother was also treated with radical hysterectomy and bilateral salpingoshotomy in her later stages, but eventually died.
Will cancer be passed on from mother to child?
Cancers associated with pregnancy or childbirth are very rare, with an incidence of 1 in 1000–2000 pregnancies [2]. The two cases described earlier illustrate that a child's tumor is caused by the transmission of a cervical tumor from his or her mother.
In both cases, the child's tumors lacked the Y chromosome and shared multiple somatic mutations, THE HPV genome, and single nucleotide polymorphisms (SNP) alleles with tumors from the mother. Moreover, the growth pattern of the peribronchial tumors of the two children suggests that the tumors are caused by inhaling vaginal fluid contaminated with the tumor at birth, leading to the occurrence of mother-to-child vaginal transmission. In other rare cases of mother-to-child transmission of cancer, offspring present with multiple disseminated metastases in the brain, bone, liver, lungs, and soft tissues; these metastases are consistent with the hypothetical spread of tumors through placental hematography.
Figure 2 Schematic diagram of mother-to-child transmission of cancer
doi: 10.1016/j.medj.2021.02.006
In fact, the direct transmission of tumors is not limited to mother-to-child transmission. In J Natl Compr Canc Netw in 2020[3], American scholars first reported that a 34-year-old male donor donated his heart, liver, kidney, and pancreas to four recipients. The heart recipient died of cancer on the 143rd day after transplantation, the liver recipient died on the 293rd day after transplantation, and a new generation of gene sequencing confirmed that the donor tumor sample was donor-transmitted.
What is the cause of mother-to-child transmission of cancer
Although cases of mother-to-child transmission of malignant tumors were first described in 1866. But so far, only modest progress has been made in its basic biology research. This is particularly important because they are associated with delayed performance in affected children. Although the biological properties of transmission are unknown, there are two main possibilities: (1) transplacental hematogenous transmission and (2) direct transmission during childbirth (by contact or inhalation) [4].
Figure 3 Cases of mother-to-child transmission of cancer doi: 10.1056/NEJMoa2030391
Figure 3 summarizes the historically reported cases of mother-to-child transmission of cancer, most of which are presumed to be placental transmission, and their speculations are mainly based on various experimental tests, such as histological confirmation, sex chromosome karyotyping, sex chromosome fluorescence in situ hybridization (FISH), microsatellite marker typing, BCR-ABL (a fusion gene) breakpoint sequencing, quantitative polymerase chain reaction (PCR) testing, etc., of which the two children reported in our article to obtain tumors are lung inhalation. This has undergone a new generation of genetic sequencing tests.
How to treat and care for expectant mothers with cancer
When a mother is diagnosed with cancer during pregnancy, there is a risk that the cancer will spread to the newborn, which is a huge challenge for expectant mothers, unborn children and the medical team. In general, the treatment of patients with cancer during pregnancy should follow the guidelines and recommendations of non-pregnant patients. However, treatment should also be personalized based on the number of weeks of gestation at the time of diagnosis, the expected prognosis of the mother, the wishes and concerns of the intended parents, and ethical requirements [5].
Diagnostic tests during pregnancy should be made without ionizing radiation. In the treatment of cancer, surgical treatment during pregnancy is selected based on the tumor entity, localization, staging and prognosis. If special precautions are used, it is safe to perform surgery on all non-abdominal or non-reproductive organs. Chemotherapy is an important part of tumor treatment in various cancer entities and should be avoided in the first trimester, but it is considered relatively safe to use chemotherapy in the second and third trimesters of pregnancy, in contrast to avoiding radiation therapy for abdominal or pelvic organs during pregnancy. Targeted therapy has become a new approach to tumor therapy at this stage, but due to the lack of evidence and experience in clinical use and safety, it is often recommended to postpone the use of targeted therapy until after delivery. At the same time, the use of hormonal therapy during pregnancy is contraindicated.
Post-delivery, fetal care for pregnancy complicated by a mother's malignant diagnosis remains a major challenge. Obstetric monitoring should follow appropriate guidelines for high-risk pregnancies and should consider possible individual side effects and individual fetal development effects from cytotoxic therapy used. During breastfeeding after cancer in pregnancy, mothers are worried about whether breastfeeding can be used, and studies have shown that breastfeeding has a variety of positive effects on mother and child, especially their relationship. All women diagnosed with cancer during pregnancy and treated in the postpartum period who are not considered contraindications to breastfeeding should receive lactation counselling and ensure the safety of breastfeeding.
Author: S.Yi
Source: Frontline of Cancer in the Health Community
bibliography:
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[2] Peccatori F.A., Azim H.A., Orecchia R., Hoekstra H.J., Pavlidis N., Kesic V., Pentheroudakis G. Cancer, pregnancy and fertility: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2013;24(Suppl. 6）:vi160–vi170. doi: 10.1093/annonc/mdt199.
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[4] Eskander R N , R Kurzrock. Maternal to fetal transmission of cancer: implications for molecular tumor testing, immune regulation, and pediatric malignancies[J]. 2021.
[5] Roxana Schwab , Katharina Anic , Annette Hasenburg. Cancer and Pregnancy: A Comprehensive Review[J]. Cancers (Basel）. 2021 Jun 18;13(12）:3048.