That’s the conclusion of two ground-breaking cases from Japan in which investigators describe lung cancer in two boys that “probably developed” from their respective mothers via vaginal transmission during birth.
“Transmission of maternal cancer to offspring is extremely rare and is estimated to occur in approximately 1 infant per every 500,000 mothers with cancer,” wrote Ayumu Arakawa, MD, of the National Cancer Center Hospital in Japan, and colleagues, in a paper published Jan. 7 in The New England Journal of Medicine.
Previous cases, of which only 18 have been recorded, have been presumed to occur via transplacental transmission, they said.
In the two new cases, genetic analyses and other evidence suggest that both boys’ lung cancers developed after aspirating uterine cervical cancer tumor cells into their lungs during passage through the birth canal.
Tragically, both mothers, each of whom was diagnosed with cervical cancer after the births, died while their boys were still infants.
“Most of the maternal-to-infant cases reported have been leukemia or melanoma,” said Mel Greaves, PhD, of the Institute of Cancer Research, London, who was asked for comment. In 2009, Dr. Greaves and colleagues published a case study of maternal-to-infant cancer transmission (presumably via the placenta). “It attracted an enormous amount of publicity and no doubt some alarm,” he said in an interview. He emphasized that the phenomenon is “incredibly rare.”
Dr. Greaves explains why such transmission is so rare. “We suspect that cancer cells do transit from mum to unborn child more often, but the foreign (aka paternal) antigens (HLA) on the tumor cells prompt immunological rejection. The extremely rare cases of successful transmission probably do depend on the fortuitous loss of paternal HLA.”
Advances in genetic technology may allow such cases, which have been recorded since 1950, to be rapidly identified now, he said.
“Where there is an adult-type cancer in an infant or child whose mother carried cancer when pregnant, then whole-genome sequencing should quickly tell if the infant’s tumor was of maternal origin,” Dr. Greaves explained.
“I think we will be seeing more reports like this in the future, now that this phenomenon has been described and next-generation sequencing is more readily available,” added Mae Zakhour, MD, of the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, when asked for comment.
In the case of the Japanese boys, both cases were discovered incidentally during an analysis of the results of routine next-generation sequencing testing in a prospective gene-profiling trial in cancer patients, known as TOP-GEAR.
How do the investigators know that the spread happened vaginally and not via the placenta?
They explained that, in other cases of mother-to-fetus transmission, the offspring presented with multiple metastases in the brain, bones, liver, lungs, and soft tissues, which were “consistent with presumed hematogenous spread from the placenta.” However, in the two boys, tumors were observed only in the lungs and were localized along the bronchi.
That peribronchial pattern of tumor growth “suggested that the tumors arose from mother-to-infant vaginal transmission through aspiration of tumor-contaminated vaginal fluids during birth.”
In addition, the tumors in both boys lacked the Y chromosome and shared multiple somatic mutations, an HPV genome, and SNP alleles with tumors from the mothers.
“The identical molecular profiles of maternal and pediatric tumors demonstrated by next-generation sequencing, as well as the location of the tumors in the children, provides strong evidence for cancer transmission during delivery,” Dr. Zakhour summarized.