Sisters hunt 'missing match': Packer family's quest to crack hereditary breast cancer mystery

Erica Packer sits in her London home waiting for test results that may never come. Every six months, she submits to mammograms and MRIs, sometimes biopsies of her breast tissue. The waiting is the hardest part—days of not knowing whether this time the tests will reveal what she fears most. She is 46, a former model and ex-wife of billionaire James Packer, but none of that shields her from the genetic shadow that has darkened her family for decades. Her mother died of breast cancer at 66. Nearly every woman on her mother's side of the family has faced the same diagnosis. Yet when Erica's older sister Jo was tested for the mutations everyone knew to look for—BRCA1 and BRCA2, the ones that made Angelina Jolie's preventative mastectomy international news—the results came back negative. The cancer was there. The gene was not. They were what researchers now call a "missing match," part of a vast and frustrating category: families where breast cancer clearly runs in the blood, but the cause remains invisible.

Jo Hunter knows this territory intimately. At 39, a nurse and mother of four living in Sydney, she received her diagnosis after routine screening suddenly showed multiple tumours. She had a double mastectomy and reconstruction. She survived—the only woman in her immediate family to do so. Her mother, Sheelah, was not as fortunate. Diagnosed at 54 in 1999 while Erica and Jo were living together in London, Sheelah initially went into remission after mastectomy, chemotherapy, and radiation. But the cancer returned. By 2007, when Erica married James Packer on the French Riviera, Sheelah was there, hiding intense back pain. Within years, the cancer had spread to her pelvis, lungs, and liver. In 2011, the same year Jo was diagnosed, Sheelah died aboard the Packer family yacht in Fiji, surrounded by her children. "She went to bed and she didn't end up getting up again," Erica recalls. The sisters were left with grief, survival, and an unanswered question: what gene was killing their family?

The answer matters because it could save lives. About 100,000 Australians live with hereditary breast cancer caused by unknown genetic mutations. Of every 100 women diagnosed with breast cancer, 10 to 15 carry an inherited mutation. Current testing can identify the cause in about 40 per cent of those cases. The other 60 per cent—including Jo and Erica—remain in the dark. "It's a bit like playing Russian roulette," Erica says of her screening routine. The uncertainty is exhausting. A year ago, she was called back from a plane already in flight with news that recent tests looked "not good." A month of anxiety followed before further testing abroad cleared her. The fear is not abstract. It shapes how she lives, how she plans, how she thinks about her three children and their futures.

But the research landscape is shifting. A decade ago, women could be tested for a handful of genetic variants. Now, up to 10 are routinely screened. At Victoria's Peter MacCallum Cancer Centre, researchers are examining another 40-plus potential mutations, using technology that can read 10 billion DNA sequences overnight. The centre has assembled an extraordinary resource: 9,000 Australian women with unexplained hereditary breast cancer, plus tens of thousands of control cases without the disease. Professor Ian Campbell, one of the centre's leading researchers, explains that this cohort is unique globally. "We have a very large number of women who have been tested for all the known genes but returned a negative result," he says. "Those women have kindly given us permission to look deeply at their genes to see if we can find an explanation." The work is painstaking, but the potential is enormous. About 150 women die each year from breast cancers caused by these unidentified mutations—deaths that might have been preventable with earlier knowledge.

Jo is undergoing new genetic testing through the Peter MacCallum centre, hoping that advances in the field will finally crack the code for her family. If she is found to carry one of the newly identified mutations, Erica will be tested too. If positive, her screening options will become clearer and more targeted. If nothing emerges, the sisters will continue as they have: vigilant, anxious, and waiting. But Jo is committed to the search. She plans to donate her genetic material to the research team, adding her data to the growing pool that scientists are mining for answers. She has become an informal ambassador for early detection, mentoring other women through breast cancer treatment and, as Erica jokes, showing them her reconstructed breasts to prove that survival and recovery are possible. The five-year survival rate for breast cancer has climbed from 76 per cent to 92 per cent since their mother was diagnosed, a testament to earlier detection and targeted treatment.

Erica speaks about genetic testing with the clarity of someone who has thought hard about what knowledge means. "If we can get these genetic causes and find out which specific one I might have, my daughters might have, anyone can have, then you can also not go through all this worry," she says. She is not seeking the spotlight—she has largely stepped away from the public eye, focusing on raising her children and her work with UNICEF and the National Breast Cancer Foundation. But she has opened her private life to journalists and researchers because the mystery matters. It matters to her daughters. It matters to the thousands of other families living under the same cloud. The search continues. Results from Jo's latest testing are still being processed. The answers may come soon, or they may take years. But for these two sisters, the hunt for the missing match is not a burden they bear alone. It is a family legacy, and a gift to everyone still waiting for their own answers.