‘Forever chemicals’ have been linked to many diseases. Are they connected to breast and gynecological cancers, too?

This story is part of a series, “Fighting ‘Forever Chemicals’: Women face pervasive PFAS risks.”

Loreen Hackett suffered two bouts of cancer before she turned 50. Cancerous cells were discovered in her cervix when she was in her 20s, leading her to undergo a hysterectomy when she was just 28. Less than two decades later, she was diagnosed again — this time with breast cancer.

Hackett, a longtime activist, said she now believes both her cancers were connected to “forever chemicals” contamination in the drinking water in Hoosick Falls, N.Y., where she has lived for most of her life and where state agencies detected problematic levels of a certain type of the compounds, known as PFOA, in the community’s groundwater supplies and private wells in 2016.

Scientists are researching the possibility of such a link between exposure to the substances, known as PFAS, and breast and gynecological cancers — though they have yet to find a definitive connection.

PFAS, which stands for per- and polyfluoroalkyl substances, are a class of chemicals found in a range of consumer products such as Teflon pans, waterproof apparel, cosmetics and stain removers. They have become pervasive in the air, water and soil due to their use in manufacturing, and are estimated to be in the blood of about 97 percent of Americans. 

Scientists have found evidence connecting numerous cancers — including testicular cancer — and other adverse health outcomes to PFAS exposure, and more findings on the issue are rapidly emerging. Establishing these links can be complicated, however.

The search for connections

“Most cancers take years to develop, and may have developmental origins that we do not clearly understand,” said Suzanne Fenton, who at the time was a group leader in the Mechanistic Toxicology Branch of the National Toxicology Program at the National Institutes of Health.

Further muddying the waters is the fact that breast and ovarian cancers include many unique subtypes, each of which could have inconsistent interactions with PFAS exposures, noted Fenton, who became the director of North Carolina State University’s Center for Human Health and the Environment in October 2023.

Patients also may be exposed to a variety of chemicals in their environment, for different amounts of time — complicating the quest “to pinpoint the role of PFAS in particular types of cancers,” she added.

Experts agree, however, that exposure to the substances could have an effect on a person’s immune system, making them more vulnerable to illnesses across the board — including cancers.

Both animal and human studies have shown that several types of PFAS can impact immune function — leading the Environmental Protection Agency (EPA) to propose using those effects as drivers for their health advisories for certain PFAS compounds, according to Fenton.

“The immune system is critically important in cancer development,” she said. 

In fact, when the World Health Organization’s (WHO) International Agency for Research on Cancer convened a working group a few years ago to define the key characteristics of carcinogens, one of the top traits included immunosuppression. 

“Those immune effects noted above may play a role in a person’s general immune function or may have effects in the tissues in which the cancer develops,” Fenton said. “PFOA and other PFAS are carcinogens.”

PFOA is a type of PFAS that has been heavily studied and that the EPA has classified as likely carcinogenic.

The WHO working group emphasized the immunosuppressive capabilities of such carcinogens by citing evidence of increased immune system dysfunction, as well as decreased “immunosurveillance” — the process in which immune cells find and target foreign tissue.

“Persistent immunosuppression presents a risk of cancer,” the report stated. “Survival of these cells and their replication to form tumors is greatly facilitated by immune suppression.”

Troubling breast development

Ruthann Rudel, director of research at the nonprofit Silent Spring Institute, described a recent shift in thinking surrounding the causes of cancer — from looking only at direct DNA damage to the idea that immunosuppressants like PFAS can increase cancer risk.

In addition, she stressed the importance of trying “to figure out why so many women are having trouble breastfeeding and why younger women getting breast cancer and puberty is starting so early — breast development in particular.”

Though scientists have not yet proven a definitive link between PFAS and breast cancer, Rudel noted that they have identified many of these same effects in lab animals exposed to the substances and other endocrine-disrupting compounds.

“There are all these problems in the human population; there are things that are changing and that we can observe,” continued Rudel, whose Massachusetts-based organization focuses on the link between environmental contaminants and women’s health. “That’s concerning, and I think we need more attention on it. And hopefully we’re moving in that direction.”

Fenton and her colleagues have long been studying the impacts of PFAS on mammary glands in animals. They published a paper on the subject, along with Erin P. Hines, a researcher in the EPA’s reproductive toxicology division, in the journal Reproductive Toxicology in 2009. 

That pioneering research described how “in-utero exposure screws up the developing mammary gland in mice,” said Linda Birnbaum, former head of the National Institute of Environmental Health Sciences and the National Toxicology Program.

“If they’re exposed in utero, then they have real difficulty nursing their pups, because their mammary gland never fully developed,” Birnbaum said.

Fenton confirmed that “mice developmentally exposed to PFOA demonstrate persistent abnormalities in breast growth in female offspring.” She stressed, however, that there have only been a few studies evaluating PFAS exposures and breast development in human girls.  

“At this time, the answer is unknown,” she said. 

Because longitudinal studies that track health impacts on a human from development through adulthood require so much time and money, Hines said scientists often look at animal toxicology studies to try to understand such endpoints. That said, if human samples are taken earlier in life, in big cohorts, follow-up can occur later in life, she explained.

“But sometimes the animal studies will give you a clue as to what you might want to look for,” Hines added.

Bolstering gynecological cancer cells

Another medical mystery impacting the human population — particularly older women — is ovarian cancer, which can oftentimes be lethal. But identifying a link between ovarian cancer development and toxic exposures during a specific life stage remains challenging because it “is much more rare than other cancers and usually a late in life disease,” Fenton explained.

“So it is difficult to ascertain that information in human studies,” she said.

Scientists do know, however, that PFAS cause ovarian cancer cells to multiply, according to Fenton, who co-authored a May 2022 paper on the subject in the International Journal of Molecular Sciences.

The authors found that some types of PFAS increase the proliferation of two ovarian cancer cell lines and disrupt the chemotherapy that aims to kill these cells.

The researchers then confirmed this data and extended their findings in a September 2022 article, which demonstrated how a type of light-based treatment could help patients overcome PFAS-induced resistance to chemotherapy.

Separate research, which Fenton also co-authored, found that the survival rate of certain endometrial cancer cells surged following exposure to specific kinds of PFAS. These cells also appeared to be less sensitive to chemotherapy, according to the study, published in Environmental Health in December.

As with other gynecologic cancers, resistance to chemotherapy plays a key role in the fatal nature of endometrial malignancies, the authors noted. 

Advocating for further research on the subject, the scientists stressed that clearer insight into the connection between environmental exposures and chemotherapy effectiveness could benefit patients who reside in PFAS-polluted communities.

“If these patient populations could be identified prior to the administration of treatment, treatment failure, which is directly correlated with decreased survival, could be prevented,” the authors added.

A decades-long battle

While a definitive connection may not yet have been made between PFAS exposure and either breast or ovarian cancer, many women — like Hackett — attribute the development of their cancers to these toxins, which have contaminated their community drinking water systems.

Hackett underwent a hysterectomy at 28 years old after doctors found cancerous cells in her cervix. She had polycystic ovarian syndrome, as well as a blood disease, for several years prior, undergoing a lengthy treatment regiment before doctors agreed to remove her uterus, a step they were reticent to take because she was so young.

Her breast cancer diagnosis came less than two decades later, when she was in her mid-40s, in 2009. Hackett decided against radiation because she felt her weakened immune system would not withstand such treatment.

“So I said, well, let’s do this,” Hackett said. “Let’s do the lumpectomy and remove the glands. And we’ll see what happens in a few years.”

While Hackett’s breast cancer has yet to resurface, she said she does now have lumps on her thyroid — which are thus far benign, according to functional blood test results. Hackett admitted in a February follow-up email that she hasn’t had her thyroid itself scanned for quite some time, as her own health issues have “taken a back seat” to other family concerns, such as her 31-year-old daughter’s recent hysterectomy. She also noted the exhaustion — and resultant avoidance — that she associates with having to go to the doctor so often.

“If you’ve gone through cancer once and gone through the whole scary part of it, you really don’t want to go through it again,” Hackett said in the original interview, noting at the time that she goes so far as to avoid medications that contain PFAS.

Boston University researchers last year identified 337 medicines that contain PFAS, also known as “organofluorine pharmaceuticals.” The scientists based their classification on the U.S. National Defense Authorization Act definition of PFAS, or any substance that contains “at least on fully fluorinated carbon” — a carbon atom on which all hydrogens are replaced by fluorines.

Among the organofluorine pharmaceuticals are some of the nation’s top prescribed drugs, including the cholesterol-reducer atorvastatin, the antibiotic ciprofloxacin, the antifungal fluconazole, and the antidepressants fluoxetine, escitalopram, citalopram and paroxetine. 

In addition to experiencing reproductive issues herself, Hackett said that her daughters have experienced similar such struggles. Like Hackett’s mother, one of her daughters is severely vitamin D deficient — a condition linked to PFOA exposure — and has had to take prescription supplements.

Hackett is aware a definitive link has not been found between PFAS and breast cancer, but she said she “wouldn’t doubt” that her cancers were, in fact, related to the contamination in Hoosick Falls, regardless. More and more research has been probing a potential connection, she contended, and stressed that breast cancer does not run in her family and that her test for the BRCA gene, which is indicative of breast cancer risk, was negative. 

A cancer incidence investigation released by the New York State Department of Health in May 2017 for the 1995-2014 date range did not identify any statistically significant elevations of cancer for any types of cancers associated with PFOA exposure, including breast, cervical, uterine or ovary cancer. 

At the time, the department said that it would update and review the cancer data for any changes in the comparative cancer profile of residents in about three to five years. 

Nevertheless, a community health questionnaire published in August 2018 by researchers at Bennington College in Vermont identified possible discrepancies with the department’s investigation. 

While the department found 12 cases of kidney cancer, no cases of testicular cancer and did not review data on thyroid disease, Bennington’s questionnaire identified 17 cases of kidney cancer, nine cases of testicular cancer and 135 incidences of thyroid disease. 

The researchers stressed that these occurrences could even be an underestimation, as only about 10 percent of Hoosick Falls residents responded to their questionnaire.

The fight for legal recognition

While scientists have linked a number of diseases to PFAS, many lawyers will only take on a personal injury case if a victim suffers from a much more limited set of ailments.

In 2004, residents of Parkersburg, W.Va., secured a settlement in a groundbreaking class-action lawsuit spurred by their exposure to PFAS from a nearby plant. That case resulted in the 2012 “C8 Science Panel,” which established a definitive link between PFAS exposure and diagnosed high cholesterol, testicular cancer, kidney cancer, ulcerative colitis, thyroid disease and pregnancy-induced hypertension.

Neither breast nor ovarian cancer made it to the list at the time, though more research has been conducted in the decade since the panel published its findings. Some attorneys will now represent victims of PFAS exposure who have other illnesses, such as pancreatic and prostate cancers, but many will still only take on a personal injury case if someone suffers from the relatively short list of diseases.

As researchers continue to investigate the possible associations between PFAS and other health impacts, Hackett posed the question: “When do these array of illnesses that are popping up more and more and more get added to that list?”

“How many studies does a lawyer need to bring to court?” she continued. “There’s no answer.”

Hackett acknowledged that there are multiple causes of breast cancer. But she denounced what she characterized as industry’s ability to “fall back on the tobacco playbook.”

“Someone can smoke and never get lung cancer,” she said. “Now, is smoking linked?”