The Rise of Early-Onset Cancers: Investigating Breast and CRC Occurrences

The American Cancer Society’s annual cancer statistics report highlighted that, in 2025, 2,041,910 new cancer cases and 618,120 cancer deaths were projected to occur.¹ Though there is a single name for the disease—cancer—there are hundreds of subtypes. Among them, 2 of the most common are breast and colorectal cancer (CRC), and unfortunately, they are on the rise in patients younger than 50.

Between the years of 2012 and 2021, an American Cancer Society survey found a 1.4% increase of breast cancer in patients 50 years or younger per year, compared with a 0.7% increase in patients 50 or older.² Breast cancer, a disease typically diagnosed in older patients, is now seeing an uptick in younger populations. Why?

For colorectal cancer, the story is similar. The American Cancer Society estimated that 108,860 patients will be diagnosed with colon cancer and 49,990 will be diagnosed with rectal cancer in the US in 2026.³ Of those combined 158,850 estimated cases of colorectal cancer (CRC), 55,230 people will die from their disease.

Since the mid-1980s, the incidence of CRC has declined due to changing patterns in risk factors and the expansion and uptake of screening in adults aged 50 and older. That rate of incidence decreased by approximately 1% every year from 2013 to 2022. Despite this, CRC is the leading cause of cancer-related death in patients under the age of 50 in the US. Among generations born since 1950, the incidence rate of CRC in patients under the age of 50 has increased by 2.9% per year, compared with 0.4% in adults aged 50 to 64 years.

CancerNetwork® spoke with Shari Goldfarb, MD, assistant attending physician specializing in breast cancer at Memorial Sloan Kettering (MSK) Cancer Center, and Marc Lehrer Greenwald, MD, the chief of Colorectal Clinical Services and surgeon-in-chief at North Shore University Hospital, about earlier cancer incidences in patients with breast cancer and CRC.

As for the potential causes of this rise in breast cancer, Goldfarb said, “We’re not entirely sure why there’s an increase in breast cancer [among] young women, but it’s likely multifactorial in nature [with] a combination of genetic and environmental factors.”

She referenced a few things that could be related to the rise in earlier diagnoses, including menses beginning prior to 12 years of age or waiting later in life to have children. More years of uninterrupted menses could be attributed to the higher breast cancer rates. Additionally, obesity, or someone reaching their adult weight earlier, plays a factor.

Similarly, Greenwald added, “It clearly is an environmental problem. We have to live healthier.” He referenced rural agrarian societies, largely unaffected by Western society, that had a much lower incidence of CRC, but when these societies ultimately immigrated to Western countries, they soon developed the same incidence of CRC that other people in their neighborhood did.

One such study by O’Keefe, et al., published in Nature Communications,demonstrated this effect, showing that rural Africans given a 2-week, low-fiber, high-fat western-style diet and African Americans given a high-fiber, low-fat African-style diet experienced “remarkable reciprocal changes” in their mucosal biomarkers of cancer risk.⁴

Differences in Molecular Subtypes and Delay in Screening

For patients under 40 years, triple-negative breast cancer is more likely to be diagnosed compared with other subtypes.⁵ This cohort, which is just under the age for recommended screening, may be diagnosed at later stages. Goldfarb noted that a woman has to be able to palpate the mass in her breast to bring it to the clinician’s attention, which by then is about 1 cm in size.

“By the time women often feel a change in their breasts, the tumors are larger, or the cancer has already spread to lymph nodes many times,” Goldfarb said.

The US Preventive Services Task Force recommends women aged 40 to 74 years receive a mammography every other year.⁶ For those who are of higher risk, including those with a BRCA1/2 gene mutation or who have a first-degree relative with that mutation, the NCCN recommends a mammogram plus a breast MRI every year starting at age 24 to 40.⁷

Goldfarb emphasized that it’s important for women to know their family histories, as that will determine when screening should begin and help catch a breast cancer diagnosis in earlier stages.

“If [patients] have a strong family history of breast cancer at young ages or have mutations that increase their risk of getting breast cancer, their imaging should be started at a much younger age. It’s important for [patients] to know what their breast cancer risk is and their family histories,” Goldfarb explained. “If someone has a risk of greater than 20% of lifetime risk of getting breast cancer, then we also add MRI screening in, and patients could get mammograms alternating with MRIs every 6 months. If someone has a family history of breast cancer at a young age, then their relative should get screening at least 10 years earlier than that woman who was diagnosed with breast cancer.”

Shifting gears, among patients with early-onset CRC, defined as CRC diagnosed before age 50, mutations in TP53, KRAS, PIK3CA, and SMAD4 were most commonly observed, which is consistent with what is observed in traditional CRC.⁸ Studies have also demonstrated that BRAF V600E mutations increase with age and BRAF mutations are less common in early-onset disease.

However, the microsatellite instability (MSI) phenotype is observed in less than 10% of CRC and late-onset CRC cases, but MSI-high (MSI-H) occurred in 10% to 30% of early-onset CRC cases.

It has also been found that hereditary tumor susceptibility syndromes occur in 16% to 35% of early-onset CRC cases, while the general genetic prevalence of CRC is 2% to 5%. Lynch syndrome, for example, is strongly associated with CRC and increases risk by up to 70%, with a 50% to 70% risk by one’s mid-40s.

“There’s no doubt that [for patients with] Lynch syndrome, who are going to be MSI-H by definition, we often see them younger,” said Greenwald.

In May 2021, the US Preventive Services Task Force made 3 recommendations for CRC screening: recommendation A, all adults aged 50 to 75 years receive screening; recommendation B, adults aged 45 to 49 get screened; and recommendation C, clinicians selectively offer screening for CRC in adults aged 76 to 85 years.⁹ These recommendations come as the task force found that screening adults aged 50 to 75 years had substantial benefit, and screening adults aged 45 to 49 had moderate benefit.

These screening guidelines were updated from previous recommendations in 2016, where the task force recommended screening for patients 50 to 75 years, not including patients aged 45 to 49.

Reproductive Health

When patients are first diagnosed with cancer, fertility may not be a topic that comes to mind to discuss with their oncologists. However, as women under 40 are increasingly being diagnosed with breast cancer, this should be top of mind for both patients and clinicians.

“Any woman who is interested in having a child that is biologically theirs prior to starting chemotherapy should undergo a variance suppression and stimulation so they can freeze eggs or embryos, whatever works best for them,” Goldfarb said.

Goldfarb has done extensive research on anti-Mullerian hormone (AMH), which is a marker for ovarian reserve. She has investigated how different types of chemotherapy can cause fertility decline, as well as a patient’s age, and who will have the biggest “hit” to their fertility.

In a 2020 study, 142 patients with breast cancer were prospectively followed before adjuvant chemotherapy initiation, as well as 12, 18, and 24 months following, wherein serum AMH was assessed.¹⁰ The chemotherapy regimens included anthracycline and cyclophosphamide, and cyclophosphamide-methotrexate plus 5-fluorouracil compared with tamoxifen.

The study results found that both chemotherapy regimens led to a decline in ovarian reserve vs tamoxifen alone (P <.0001). At 12 months, AMH levels sharply declined, but there was no significant recovery from 12 to 18 and 18 to 24 months.

Alternatively, the POSITIVE trial wanted to examine whether women paused their endocrine therapy for a maximum of 2 years to attempt to get pregnant, have a baby, and resume treatment.¹¹ At the 71-month median follow-up, 497 patients who were followed for pregnancy outcomes, 76% achieved at least 1 pregnancy during the trial, and 91% had at least 1 live birth.

“In the short term, the data show that these women did not have a worse prognosis, but I would caution people that many of the [patients] who discontinue their endocrine therapy early on have earlier-stage disease. We only have short-term outcomes right now, so we do have to follow patients for a longer period to make sure that it is truly safe. Based on old data, we know that when women took 5 years of endocrine therapy and completed their therapy, [they] then were able to get pregnant post-treatment and post-endocrine therapy. Compared with their cohort of women who did not get pregnant, they had the same or even better outcomes. There’s a healthy mother bias,” Goldfarb explained.

Positive Patient Stories

Amidst the unfortunate rise in cancer incidence for younger patients, Greenwald spoke about some of his more recent and positive cases. At the time of the discussion, Greenwald had seen 2 young patients with CRC within the past month. The first was a 22-year-old who had just graduated from an Ivy League college. She had abdominal pain, a partially obstructing colon cancer, and no family history of CRC. The patient underwent a colonoscopy, and her colon proximal to the lesion, which was in the descending colon, could not be evaluated. Her bowels moved every 1 to 2 days.

Greenwald suggested a subtotal colectomy because it decreases the length of the colon, and they were unable to see the proximal colon because of the obstruction, and that was what they did.

“Her bowel function is pretty good. Even after a month, she's only moving about 2 or 3 times a day, and it's semi-formed. It's only going to get better,” he said.

The second patient was a 35-year-old with a descending colon cancer that was partially obstructing, and presented after a colonoscopy. He had several first-degree connections with family history across a couple of generations, and met Lynch syndrome criteria by the old, pre-genetics criteria.

This patient was recommended the same procedure—subtotal colectomy—for the same reasons as the previous patient. “Both of these people are going to do quite well,” he added.

Including Survivorship Care Into Daily Practice

“The patient is not the disease. The patient is a person with a problem,” said Greenwald. It’s a “good” physician’s job to not just treat the disease, but to treat the entire patient. With many advances in technology and treatment, in some cases, it has become possible to spare patients invasive treatments. One consideration Greenwald brought specific attention to was how an older patient, who may be incontinent or in a wheelchair, would be treated differently than a young person with good control or who is single and looking to meet a life partner.

As a surgeon, one discussion he may have with patients is the need for a temporary or permanent ostomy. Of course, as he said, “the cure is the cure”, and if there’s a treatment needed to give a patient the most positive outcome, there is little that can be done against that, but clinicians try strive to provide patients comfortable lives, even after treatment. That’s why it’s so important to consider all faculties at a treatment center.

While patients are often seeing the main specialties like medical oncology, radiation, or surgery during their initial visits and even during treatment, there are other areas like social work, psycho-oncology, and sexual health services.

Goldfarb noted that after a young woman gets a diagnosis, she is often referred to a reproductive endocrinologist, followed by a social worker. She explained that the social worker can help to discuss their cancer diagnosis with their children, parents, and even colleagues.

Additionally, Greenwald highlighted the enterostomal team at North Shore University Hospitals, which provides patients with the help and support services they need to turn patients into proud survivors.

“If you look on the internet, you could find young women flashing off their ostomy at the beach, because they are a proud survivor, and that was their only option. They are happy they’re alive,” Greenwald said.

Regarding sexual health, Goldfarb and her team have found that women, often upfront, are not ready to be referred to a specialist. It often takes women experiencing vaginal atrophy or dryness for them to seek counseling. Because of these experiences, she has opened a clinical trial (NCT05910294) focused on preventative counseling for these adverse effects from treatment.

“When patients get through their treatment, they get through their surgery, maybe they get through the radiation, then they’re feeling better and their energy is coming back. That’s in that post-treatment phase when we depend on our psychiatry colleagues the most, because that’s when [a patient’s] adrenaline is down, and now they’re coping with their cancer diagnosis and everything it comes with it,” Goldfarb noted when highlighting the psycho-oncology department at MSK.

The Next Steps

As these new trends take shape in breast and colorectal cancer, experts across oncology have been conducting research and developing new tools to combat them. It came as no surprise that Greenwald, as a surgeon, emphasized the importance of the new minimally invasive surgery technology being released, as well as some of the new robotic platforms. With those praises, he noted the importance of being wary and paying attention to what is real and what is fake, especially in an industry where there could be a monopoly. On a different note, he coined checkpoint inhibitors as a “game changer” for patients with MSI-H CRC.

In breast cancer, Goldfarb runs the Young Women with Breast Cancer program at MSK, designed for patients 45 years old and younger who are undergoing treatment or in the survivorship phase.¹² The program is designed for those younger patients, as they are in different phases of their lives compared with older patients undergoing treatment. Those who are younger may be finishing school, starting a family, or venturing into their careers.

However, while there are many resources available to help patients during this difficult time, Goldfarb highlighted that patients need to advocate for themselves, “I would empower young women to always advocate for themselves. If they feel something abnormal, make sure they bring it to a doctor’s attention. Make sure they get imaging if they need it, or biopsy if they need it. Don’t wait, because early diagnosis helps with finding things at a younger, earlier stage, with a better prognosis.”

References

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11. Pagani O, Niman SM, Ruggeri M, et al. LBA12 5-year follow-up results from the POSITIVE (Pregnancy Outcome and Safety of Interrupting Therapy for Women with Endocrine Responsive Breast Cancer) trial. Ann Oncol. 2025;36(2):S1557. doi:10.1016/j.annonc.2025.09.022
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