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As cancer rates soar among young people, experts all over the world are launching major investigations in an attempt to discover what's behind the rise.
But there's another cancer question that is equally puzzling: why do some types of cancer continue to come back?
If five years have passed and there is no sign of cancer, patients are usually considered cured — as few see their disease return.
But with some types of breast cancer, as many as a quarter of women will be diagnosed with the disease again, sometimes decades in the future. Now, medical experts across the globe are hunting for the reasons why.
Dr Francisco Contreras, director and president of Oasis of Hope Hospital in Mexico, told DailyMail.com: 'The thorn on the side of oncology is the recurrence of cancer after successful treatment.'
'This problem varies widely depending on types of cancer and stage, how aggressive the malignancy is, and the type of therapy given.'
On average, breast cancer recurs anywhere from three to 25 percent of the time. Experts believe young, obese women are most at risk, as well as those with more aggressive types
Breast cancer deaths have slowly decreased, but cases in young women are gradually increasing year over year, federal data has found
Breast cancer, the most common form of the disease in women, affects more than 300,000 American women every year and kills over 42,000.
Death rates have steadily decreased over time, from roughly 48 deaths per 100,000 women to 27 per 100,000 over the last 40 years, thanks to a slew of new treatments like hormone therapies and drugs that help the immune system kill cancer cells.
However, the Breast Cancer Research Foundation estimates that diagnoses in women under 50 have increased by two percent per year for the last five years.
While these advances have proved highly effective at destroying the disease, they haven't stopped it returning many years later.
Dr Contreras noted that he recently saw a patient whose breast cancer returned 25 years after she was declared cancer free.
One possible reason, he suggests, for a small number of women, could be the recent move to more minimally-invasive techniques for treating the disease — such as surgically removing a lump, rather than the whole breast.
While this can improve quality of life, the disease can recur in remaining tissues.
Another reason could be to do with hormones, namely the female sex hormone estrogen. Roughly 80 percent of breast cancers are ER positive, meaning cancer cells have receptors that allow estrogen to grow.
It's estimated that in about a quarter of patients with this condition, the cancer cells remain and then wake up years, even decades later.
Additionally, one in five breast cancers are genetically programmed to create higher levels of the protein HER2, which has been shown to help breast cancer cells grow quicker. These breast cancers are known as HER2 positive.
In ER positive breast cancer, estrogen stimulates the division of cells in the breast, which increases the risk of cancerous mutations in the DNA of the tissue.
While most patients with this type of disease take hormone-suppressing drugs after cancer treatment to account for this risk, some patients stop taking them too soon, and they aren't always effective.
Most patients with HER2 positive breast cancer don't experience recurrence, the HER2 gene is known to mutate and cause cancer to come back and spread further.
There are also other types of breast cancers that have long been known to be particularly aggressive types.
Triple-negative breast cancer (TNBC), for example, is known to be fast-growing, with some research suggesting up to 50 percent of patients expereince recurrence, and 37 percent die within five years of undergoing surgery.
TNBC, which accounts for 10 to 15 percent of all breast cancers, also do not have estrogen or progesterone receptors or higher levels of HER2, meaning that there are fewer options for targeted treatment.
Inflammatory breast cancer, meanwhile, only accounts for one to five percent of breast cancers. Unlike most forms of the disease, it doesn't cause a lump and tends to occur in women under 40.
Most women are diagnosed with breast cancer over age 60, but experts warned that younger women are more likely to have recurrence
Shannen Doherty (left) was first diagnosed with breast cancer in 2015, going into remission in 2017. However, her cancer recurred in 2020, and she is now in stage four. Olivia Newton-John (right) was first diagnosed with breast cancer in 1992. She died of the disease nearly three decades later in 2021
Dr Anne Peled, breast cancer surgeon and co-director at Sutter Health Pacific Medical Center in San Francisco, told DailyMail.com: 'Certain breast cancer types like HER2 positive and triple negative breast cancers are more likely to recur and are also more likely to recur in the first few years after diagnosis.'
'While this makes getting through the early years after treatment much more stressful for our patients with these types of breast cancers, we love celebrating with them once they’ve gotten through these years cancer free, as their risk of ever getting cancer again after that is very low.'
However, she noted that while ER positive and HER2 negative breast cancers are overall less likely to occur, the disease is more likely to come back decades later.
Women diagnosed with breast cancer before age 35 are also thought to be at an increased risk of recurrence, as they are more likely to have aggressive forms of the disease and be diagnosed at later stages.
Dr Jennifer Son, breast surgeon at MedStar Georgetown University Hospital in Washington DC, told DailyMail.com: 'The younger a patient is the higher risk of recurrence because they have many more years to live.'
She also noted that, on average, obese women are about 18 percent more likely to have breast cancer recurrence. This is because fat cells produce estrogen, which helps HER2 positive tumors grow.
It's also thought that in some cases, treatment shrinks tumors so small that they can't be picked up on follow-up scans, so they can regrow.
Breast cancer recurrence can present unique challenges, experts have also warned.
For example, Dr Son noted that 'if patients have a recurrence and have already had a lumpectomy and radiation, they usually cannot get radiation again in the same breast.'
And secondary tumors can come back as more aggressive, Dr Contreras said, as they can become resistent to previously used treatments like chemotherapy and radiation.
Secondary tumors can also spread to other areas like the lymph nodes, requiring more aggressive protocols.
However, thanks to targeted therapies, many women live for several years — and even decades — with later stage breast cancer.
Recent data from the Fred Hutch cancer center shows 17 percent of women with breast cancer that has spread to other organs have been living with the disease for more than 10 years.