Unique Considerations for Patients with Early-onset Breast Cancer

While breast cancer is most frequently diagnosed between the ages of 65 and 74, it is becoming more common in younger women, with about 10% of all new cases found in women under 45 years of age.  

It is unclear why the incidence of early-onset breast cancers is rising, but some hypothesize that increasingly sedentary lifestyles, obesity, environmental exposures and delayed age of childbearing could be contributing factors.  

At the 2024 San Antonio Breast Cancer Symposium (SABCS), held December 10-13, researchers discussed some of the unique considerations surrounding the treatment and management of breast cancer in younger patients, including their high risk of secondary cancers and the impacts of treatment on menopause and fertility.  

Is Prophylactic Surgery Beneficial for BRCA Carriers With Early-onset Breast Cancer? 

One study, presented by Matteo Lambertini, MD, PhD, from the University of Genova-IRCCS Policlinico San Martino Hospital in Italy, explored the benefits of risk-reducing surgeries in patients with germline BRCA mutations who were diagnosed with breast cancer before age 40.  

Individuals with germline BRCA mutations have an increased lifetime risk of developing breast and ovarian cancer, respectively, and some—particularly those who are young—opt to undergo risk-reducing mastectomy (RRM) and/or risk-reducing salpingo-oophorectomy (RRSO). 

While the benefit of such prophylactic surgeries has been demonstrated for BRCA-mutation carriers who have never been diagnosed with cancer, their impact for those with a history of early-onset breast cancer has been less clear, explained Lambertini.  

“Considering the unique traits and needs of this younger population, and their high risk for secondary malignancies, it is critical to understand how risk-reducing surgeries affect patient outcomes so that the risks and benefits of these procedures can be carefully weighed,” he said in a press release about the study.  

Both RRM and RRSO can adversely affect a patient’s quality of life, Lambertini explained, adding that RRSO also leads to infertility and early menopause, which can be particularly difficult for BRCA carriers with prior breast cancer since they are not eligible for the hormone replacement therapies that help mitigate menopause symptoms.  

To study the association between RRM and/or RRSO and survival outcomes, Lambertini and colleagues conducted a retrospective analysis of 5,290 patients with germline pathogenic or likely pathogenic variants of BRCA who were diagnosed with breast cancer at the age of 40 or younger.  

Among these patients, 3,888 underwent at least one risk-reducing surgery, and 1,402 patients did not undergo either surgery. 

The researchers found that undergoing RRM and/or RRSO was associated with improved outcomes. After a median follow-up of 8.2 years, patients who had a RRM had a 35% lower risk of death and a 42% lower risk of breast cancer recurrence or second primary malignancy, and patients who underwent a RRSO had a 42% lower risk of death and a 32% lower risk of breast cancer recurrence or second primary malignancy.  

“This global study provides the first evidence that risk-reducing surgeries improve survival outcomes among young BRCA-mutation carriers with a prior history of early-onset breast cancer,” said Lambertini. “We believe that our findings are critical for improving the counseling of BRCA-mutation carriers with early-onset breast cancer on cancer-risk management strategies.” 

The Who, Why, and When of Ovarian Suppression in Young Patients 

Some patients with breast cancer may be treated with ovarian suppression, which shuts off the ovaries’ ability to make estrogen. Ovarian suppression can be permanent (in the case of surgical removal of the ovaries or ovarian radiation) or temporary (when drugs are used to block estrogen production). For young women, the decision to undergo ovarian suppression can be complex. The treatment causes early onset of menopause, which means patients have to prematurely manage the corresponding physical symptoms, and it can have implications for family planning with even temporary ovarian suppression usually lasting for several years. 

During an educational session on breast cancer in young patients, moderated by Lambertini, Prudence Francis, MD, from Peter MacCallum Cancer Centre, discussed the multitude of considerations for ovarian suppression in young patients—who is likely to benefit, why ovarian suppression might be beneficial, and when and for how long to suppress ovarian function. 

Who: Francis explained that a patient’s risk of disease recurrence, tumor biology, planned treatments, and whether she plans to have more children factor into clinical decisions. Premenopausal patients who have chemotherapy-induced amenorrhea (loss of menstruation), favorable tumor biology, low risk of recurrence, or are planning to undergo chemotherapy, adjuvant aromatase inhibition, or adjuvant CDK4/6 inhibition are among those who might be recommended ovarian suppression. And while ovarian suppression is typically considered for patients with estrogen receptor (ER)-positive breast cancer, it can also be beneficial for certain patients with ER-negative disease, Francis noted. 

Why: For young patients who have chemotherapy-induced amenorrhea, for instance, ovarian suppression can prevent a reversal of amenorrhea upon starting aromatase inhibitors; this is important because resuming menstrual cycles could make aromatase inhibition less effective and increase the patient’s risk of an unexpected pregnancy. Ovarian suppression may also reduce the risk of serious side effects from adjuvant therapy, with evidence suggesting that it lowers the risk of venous thrombo-embolism associated with CDK4/6 inhibitors. 

When: Francis outlined recommendations for the timing of ovarian suppression for different groups of women. For those who are still looking to have children, ovarian suppression should begin before chemotherapy; for those who do not plan to have more children, ovarian suppression should begin after chemotherapy. The timing of ovarian suppression may also depend on the age of the patient and whether oral endocrine therapy is planned. Ovarian suppression is typically continued for up to five years but may be safely paused for two years to allow patients to conceive naturally or through assisted reproductive technology.  

Additional Considerations for Understanding and Treating Early-onset Breast Cancer 

The diverse presentations included in the educational session illustrated additional implications of breast cancer development and management at a young age—from the age-related biological events that promote cancer initiation to the unique considerations for treatment and survivorship. 

One presentation, delivered by Camila dos Santos, PhD, of Cold Spring Harbor Laboratory, touched on how pregnancy and urinary tract infections—both more common in younger women—alter breast tissue and increase the risk of breast cancer, findings that may inform efforts to prevent or treat breast cancer. Urinary tract infections, for example, alter gene expression in immune cells throughout the body, which suppresses collagen remodeling in connective tissue, including in the breast, and can lead to tumor-promoting tissue changes. 

In another presentation, Jennifer Sheng, MD, of Johns Hopkins University, discussed some of the challenges that young breast cancer survivors face, including issues surrounding fertility, psychosocial health, sexual health, and treatment adherence, among others.