Genetic testing changes the course of hereditary cancer in a family observed for 20 years
A case report published in the journal CA:A Cancer Journal for Clinicians shows how genetic analysis and molecular biology studies helped confirm the diagnosis, guide preventive surgeries, and define personalized surveillance strategies across generation.
image:
Engineer Marcos Vinícius Sampaio Vieira (in the blue shirt) with his wife and children in a photo taken last June: Five years after being treated for medullary carcinoma, molecular tests revealed that Marcos carried an inherited mutation in the RET gene. This finding led to the decision to have his young children undergo preventive surgery to completely remove their thyroids, which prevented cancer from developing in the next generation
view moreCredit: Marcos Vieira
Marcos Vinicius Sampaio Vieira, a 56-year-old Brazilian engineer, spent a month in Italy to say goodbye to his older brother, who died in June from intestinal cancer. This loss reignited an untold story spanning generations of the Vieira family, which had only begun to be investigated 21 years earlier when Marcos, at age 35, discovered three nodules in his thyroid during a routine visit to a cardiologist – one of them measuring four centimeters.
“I was referred to an endocrinologist, and at first, they thought it was a goiter – an abnormal enlargement of the thyroid gland – because my hormone levels were normal. But I was suspicious and asked for a biopsy,” Vieira recalls.
The biopsy revealed a seemingly common malignant tumor that could be cured with surgery and iodine therapy. However, it was only after his thyroid was removed that Marcos was diagnosed with medullary carcinoma, a rare and aggressive cancer with a strong genetic component that may or may not be hereditary.
In 2005, after having his thyroid removed, Marcos underwent a second procedure, cervical dissection (clearing of the lymph nodes). This more invasive surgery left Marcos with difficulty moving his arm for a few months and was intended to “clear” the neck region, examine the lymph nodes, and determine whether the disease had spread.
“The result was that I had no metastasis, which was wonderful news. So I went on with my life,” he says.
However, moving on with life in his case meant constant monitoring. Three years after his thyroid was removed, his blood test results showed abnormalities, and a CT scan detected metastatic lesions in his liver. “Although it was something I knew could happen, it was a very difficult time that I hadn’t expected since I’d never had any symptoms,” he says.
Since medullary carcinoma can be genetically inherited, Marcos’s family was investigated to determine if his brother, two children, and two nieces might develop the same disease.
Initial tests came back negative for all relatives tested. However, that sense of security was shattered when Marcos’s brother began developing visible nodules on his thyroid. Further testing at referral centers confirmed that the initial results were false negatives and that the family could develop the same type of cancer as Marcos.
In 2010, Marcos, who was then volunteering with a research group at the São Paulo State Cancer Institute (ICESP), underwent a molecular test that confirmed the diagnosis. The thyroid tumor was diagnosed as medullary carcinoma and was discovered to be caused by an inherited mutation in the RET gene, which is known for having nearly complete penetrance. In medical terms, this means virtually all carriers of this hereditary mutation will develop cancer over the course of their lives unless they undergo preventive surgery. The condition was no longer individual, but rather a problem affecting the entire family.
Another important point is that medullary carcinoma can spread to other organs, forming metastases. In Marcos’s case, in addition to the nodules discovered in his liver in 2008, he developed tumors in his spine. However, local treatment was possible in his spine about two and a half years ago using a cryoablation technique to eliminate the tumor.
“Medicine has changed profoundly with advances in molecular biology. The discovery of the RET gene in 1993 revolutionized the management of these patients. We’ve moved from reactive interventions to preventive and precision strategies,” says Ana Hoff, head of Endocrinology at ICESP and the University of São Paulo Medical School (FM-USP), as well as one of the authors of the article published in May in the journal CA: A Cancer Journal for Clinicians. The article uses Marcos’s story as a central theme to discuss how advances in molecular biology have transformed the management of such a specific disease.
According to Hoff, Marcos’s case illustrates this change. “While he and his brother faced metastatic diseases due to late diagnosis, their children and one of their nieces, identified through genetic screening, underwent prophylactic surgeries and remain disease-free,” she says.
The study, published in CA – the journal with the world’s highest impact factor (232), surpassing all other scientific publications – uses a new methodology called Big Picture Evidence, which synthesizes decades of scientific knowledge in a structured way. “We wanted to map everything that was already known about the use of genetic testing in the management of medullary carcinoma. We reviewed everything from the discovery of RET to the current challenges of incorporating the test into clinical practice,” says Lucas Leite Cunha, a professor at the São Paulo School of Medicine of the Federal University of São Paulo (EPM-UNIFESP) and advisor in the Graduate Program in Evidence-Based Health. He is also the author of the study, which was supported by FAPESP.
Unlike studies based on laboratory data, the article uses an emblematic clinical case – that of the Vieira family – as a starting point for a comprehensive literature review. The study incorporates the perspectives of various specialists, including a geneticist, an endocrinologist, a surgeon, an oncologist, and a pathologist, as well as the patient’s own perspective, which is unusual.
“It was a two-year project, bringing together research histories, patient stories, technical advances, and implementation barriers. This panoramic view allowed us to understand how genetics shapes the entire clinical journey of the patient and their family,” says Cunha.
Confirmation of the mutation led Marcos to reflect on the past and, more importantly, consider the future. His father had died of prostate cancer in the 1990s. “Preserved tumor samples revealed that he also had the mutation,” says the engineer.
However, Marcos’s most difficult decision involved looking ahead. His children, who were seven and ten years old at the time, needed to undergo preventive surgery to completely remove their thyroids – the only way to prevent cancer from developing.
“It was a very difficult decision, but it turned out to be the right one. It’s a burden you don’t want to pass on to your children. I remember asking Dr. Ana Hoff what she would do if they were her own children. She replied that she would operate. So we went ahead with the surgery. My niece also had her thyroid removed,” he says.
Now adults, Marcos’s two children are studying to become doctors. “Perhaps this whole story has influenced them. My daughter is in her pediatric residency, and my son just started college.”
The article emphasizes that medullary thyroid carcinoma is an ideal model for precision oncology. “The ability to identify at-risk individuals decades before clinical onset allows us to transform a potentially lethal hereditary condition into a preventable disease,” says Hoff. “The challenge now is to democratize access to molecular testing and targeted therapies beyond major academic centers.”
In Brazil, research on the management of medullary thyroid carcinoma is currently led by a consortium of research institutions (BRASMEN), including UNIFESP, USP, and the State University of Campinas (UNICAMP), with financial support from agencies such as FAPESP.
For Marcos, the molecular test ended a cycle that had persisted silently through generations of his family. “Expanding access to these tests would allow other families to experience the hope of early intervention.”
About São Paulo Research Foundation (FAPESP)
The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe
Article Title
Medullary thyroid carcinoma and RET molecular testing: A virtual tumor board on clinical decision-making
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