Sugar and cancer – what you need to know

Breast Cancer Surgery Not Always Necessary, New Research Suggests

A pair of studies suggest some patients with early-stage breast cancer may be able to safely avoid certain surgeries, adding to ongoing conversations about how aggressively to treat low-risk cancers. 

The research was presented Dec. 12 at the San Antonio Breast Cancer Symposium.

One study involving 950 patients found women with ductal carcinoma in situ who were closely monitored were no more likely to develop invasive breast cancer than those who underwent surgery. Participants were randomly divided into two groups: one received the current standard of care — surgery with or without radiation — while the other followed active surveillance, which involved mammograms every six months.

Those in the active monitoring group could opt for surgery at any time, and most women in both cohorts received hormone therapy to prevent cancer growth. After two years, rates of invasive cancer were similar in both groups: about 6% in the surgery group and 4% in the monitoring group, according to the findings published in JAMA.

DCIS occurs when cells lining the milk ducts become abnormal while the surrounding breast tissue remains healthy. Often called "stage-zero" breast cancer, DCIS does not always progress to more advanced or invasive cancer. About 50,000 women in the U.S. Are diagnosed with DCIS annually.

"Many women wonder — 'Do I really need to do this to myself?' - when they're faced with surgery and possibly radiation to remove DCIS," Shelley Hwang, MD, an author on the study and a breast cancer surgeon at Duke Cancer Institute, said in a news release. "These early results from our study give us reassurance that active monitoring is safe in the short term and that the cancers that are diagnosed during active monitoring are detected at an early stage." 

Some physicians who were not involved in the research cautioned that the study period was too short to draw firm conclusions, The Wall Street Journal reported. Researchers acknowledged longer-term follow up is needed, and plan to conduct additional analyses after five, seven and 10 years. 

A separate study published in The New England Journal of Medicine found women with early-stage breast cancer scheduled for breast-conserving surgery and who opted not to have their lymph nodes removed had similar outcomes to patients who did undergo lymph node removal surgery. Five years later, 92% of patients in both groups were still alive and cancer free. Women having breast cancer surgery often have a sentinel lymph node biopsy where lymph nodes in the armpit are removed to check if cancer is spreading, though the removal can cause chronic pain and arm swelling. 

The findings add to conversations in the oncology community about whether certain low-risk cancers are overtreated. For example, physicians typically recommend careful monitoring for low-risk prostate cancers, which account for around one-quarter of men diagnosed with prostate cancer. Evidence has demonstrated this is an effective way to manage low-grade prostate cancer, while sparing patients from treatment side effects and cost. However, around 40% of patients with a lower-grade diagnosis opt for more aggressive treatment options, prompting debates about whether the lowest-risk cancers should be classified as cancer at all. 

New Duke Study Could Mean Fewer With Early-stage Breast Cancer Would Face Surgery, Radiation

A newly released study is challenging the way doctors commonly treat patients with ductal carcinoma in situ (DCIS), known as stage zero breast cancer.

DCIS cancer cells are confined inside a milk duct in the breast and haven't yet spread to other tissue.

Duke Surgical Oncologist Dr. Shelley Hwang explained common treatment includes surgery with or without radiation.

"About 1/3 of women ended up getting a mastectomy, and a lot of those women got a double mastectomy because they were just very frightened," said Hwang. "I  think a lot of the treatment around DCIS was based on an incomplete understanding of what their future risk for cancer would be."

Hwang spearheaded a study to research if active monitoring could be a viable alternative to save patients the pain of surgery and radiation.

The initial findings in the Comparison of an Operation to Monitoring with or without Endocrine Therapy (COMET) study were published this week.

"There are a group of cancers called solid tumors where they grow as cancers in organs all over the body, and breast is one of those. A lot of these solid tumors have a precancerous condition that kind of precedes the development of invasive cancer," Hwang explained.

Hwang has been researching these precancerous cells for about two decades and has a background in epidemiology.

The ongoing study followed 995 women diagnosed with low-risk DCIS.

Some were assigned active monitoring while others were assigned to the standard care group.

Those in the active monitoring group underwent biannual breast exams and mammograms. These patients were only treated with surgery and radiation if it was determined their DCIS progressed to an invasive cancer.

"We actually found there was no significantly higher risk of having cancer in the patients who had active monitoring. In fact, we actually found they had a slightly lower risk of having cancer than the patients who had surgery right away," shared Hwang.

The data reported 19 patients in the active-monitoring group developed invasive cancers, compared to 27 patients who had surgery with or without radiation right away.

"We don't know much about what happens at that pre-cancer step. What's becoming really clear in the research that's coming out is not all precancers become cancer," said Hwang.

The American Association for Cancer Research reports only 20% of DCIS cases will become invasive cancers.

Hwang said the research could eventually lead to a change in how the medical community treats those diagnosed with DCIS.

"It will hopefully change how people talk about the disease. I think cancer is just what we've been calling it because we don't know what to call it," said Hwang. "I call it 'pre-cancer' because that gives people a little bit of perspective that they don't have cancer yet. I just hope the discussions around this diagnosis change a little bit and becomes less scary for patients."

Hwang added avoiding unnecessary surgery would save patients from an immeasurable amount of psychological trauma that often comes with a single or double mastectomy.

"I do want to reassure patients, if you've been diagnosed with DCIS already and you are one of the ones who had a mastectomy or double mastectomy or radiation, we always do the best we can with the information that we have. But we always need to continue to try to do better," Hwang added.

The research is exciting to patients who were previously diagnosed with DCIS, like Laura Colletti.

When a 2014 biopsy revealed she had DCIS, Colletti was connected with Hwang.

She eventually opted to forgo surgery and opt for active monitoring in addition to endocrine therapy.

"After talking to my husband and researching it and talking to Shelley, I just felt so much better," said Colletti. "I felt like I do have other options, and the options seem really suitable to me."

Colletti told WRAL making that decision has alleviated a lot of stress in her day-to-day.

A decade later, her scans remain clear.

"I'm 10 years out from that diagnosis, and I'm fine. Everything is normal. It's been great," Colletti said. "I feel like that moment was so fortuitous, just meeting her at that exact time."

Colletti said she has hope Hwang's continued research in the space will develop more options for other patients like her.

"I hope this is the beginning of a transformation of the standard of care. In this country, to change a standard of care for a certain illness or disease, it takes forever," said Colletti. "I think it's going to be a process but this is the beginning. Women in this situation need more choices and options."

Additional data will be collected from those enrolled in the COMET study at both the 5- and 10-year marks of the study.

Hwang reminds patients even if active monitoring becomes more widely used, it won't be an option for every patient.

"These results are exciting and it changes how we're going to think about this disease and I hope other pre-cancers as well. I do want to caution it's not for everybody with a diagnosis with DCIS," said Hwang. "It's important to remember we only enrolled patients with lower-risk DCIS and that's about half the population who gets diagnosed every year. "

Older Patients With Early Breast Cancer May Have Worse Immune Side Effects

Patients with early breast cancer who are older may experience high-grade immune-related side effects after receiving immune checkpoint inhibitors.

Older patients with early-stage breast cancer who receive immune checkpoint inhibitors may experience a higher risk of severe immune-related side effects.

Older patients who previously received immune checkpoint inhibitors for early-stage breast cancer may have an increased risk of developing high-grade immune-related side effects, according to findings from a multi-institutional study presented at the 2024 San Antonio Breast Cancer Symposium (SABCS).

Specifically, the occurrence of any- and high-grade immune-related side effects were 72.6% and 18.9%, respectively, in patients with early-stage breast cancer who received immune checkpoint inhibitors. Among the patient population, Dr. Alexis LeVee and colleagues demonstrated the distribution of any- and high-grade immune-related side effects. Regarding any-grade immune-related side effects, none were observed in 27% of patients, one was observed in 43%, two was observed in 23%, three was observed in 5.7%, four was observed in 1.2% and five was observed in 0.2%. Of note, no high-grade immune-related side effects occurred in 81% of patients, one was observed in 17% and two were observed in 1.7%. There were no high-grade immune-related side effects reported after two.

"The rate of [immune-related side effects] may be higher in our study compared [with] that observed in KEYNOTE-522 due to differences in patient populations, with our study consisting of older patients who may have had more comorbidities," LeVee and colleagues wrote in the poster presentation.

LeVee is chief fellow, Hematology and Medical Oncology at City of Hope in Los Angeles, California.

Glossary:

Immune checkpoint inhibitors: a type of immunotherapy that blocks checkpoint proteins, which are responsible for causing cancer growth.

KEYNOTE-522 was a phase 3 trial that evaluated previously untreated patients with stage 2 or 3 triple-negative breast cancer, a study that was published in The New England Journal of Medicine. Patients on the trial were either treated with neoadjuvant (presurgical) therapy with Keytruda (pembrolizumab) plus paclitaxel and carboplatin (chemotherapy) or placebo (inactive drug) plus paclitaxel and carboplatin. The incidence of treatment-related side effects of grade 3 (severe) or greater was 78.0% in the Keytruda group versus 73.0% in the placebo group.

The multi-institutional study included patients with stages 1 to 3 breast cancer who received immune checkpoint inhibitors at four academic institutions between 2014 and 2024.

Regarding patient demographics, any-grade immune-related side effects occurred in 307 patients and did not occur in 116. Median age was 51.0 and 50.5 in patients from the any-grade immune-related side effects cohort who did and did not have any-grade immune-related side effects, respectively. Regarding menopausal status, 155 patients (50.5%) and 61 patients (52.6%) were premenopausal among those who experienced any-grade immune-related side effects and those who did not, respectively. Postmenopausal status was reported in 148 (48.2%) and 52 (44.8%) patients, and unknown menopausal status was reported in 4 (1.3%) and 3 (2.6%) patients. Body mass index (BMI) was 27.0 and 27.3. Among patients who did and did not experience any-grade immune-related side effects, respectively, 199 (64.8%) and 56 (48.3%) of patients were White, 25 (8.1%) and 27 (23.3%) were Hispanic, 26 (8.5%) and 10 (8.6%) were Black, 30 (9.8%) and 12 (10.3%) were Asian or Pacific Islander, 1 (0.3%) and 2 (1.7%) were American Indian, and 26 (8.5%) and 9 (7.8%) were unknown.

Smoking status and comorbidities were also observed among patients in the study. In patients from the any-grade immune-related side effects cohort who did and did not experience any-grade immune-related side effects, respectively, 12 (3.9%) and 4 (3.4%) patients were current smokers, 101 (32.9%) and 32 (27.6%) were former smokers, 193 (62.9%) and 80 (69.0%) were never smokers, and 26 (8.5%) and 9 (7.8%) were unknown. Autoimmune disease was reported in 30 (9.8%) and 5 (4.3%), diabetes mellitus in 35 (11.4%) and 12 (10.3%), hypertension in 85 (27.7%) and 34 (29.3%), hyperlipidemia in 51 (16.6%) and 15 (12.9%), CKD in 12 (3.9%) and 1 (0.9%), preexisting lung disease 102 (33.2%) and 35 (30.2%), and coronary artery disease in 12 (3.9%) and 2 (1.7%).

Patient demographics for the high-grade immune-related side effects cohort included 80 patients who experienced high-grade immune-related side effects and 343 who did not experience high-grade immune-related side effects. Median age was 53.5 and 50.0 in patients from the high-grade immune-related side effects cohort who did and did not experience high-grade immune-related side effects, respectively. Regarding menopausal status, 34 patients (42.5%) and 182 patients (53.1%) were premenopausal among those who experienced high-grade immune-related side effects and those who did not, respectively. Postmenopausal status was reported in 45 (56.2%) and 155 (45.2%) patients, and unknown menopausal status was reported in 1 (1.3%) and 6 (1.7%) patients. BMI was 26.1 and 27.4. Among patients who did and did not experience high-grade immune-related side effects, respectively, 54 (67.5%) and 201 (58.6%) of patients were White, 5 (6.3%) and 47 (13.7%) were Hispanic, 3 (3.8%) and 33 (9.6%) were Black, 11 (13.8%) and 31 (9.0%) were Asian or Pacific Islander, 1 (1.3%) and 2 (0.6%) were American Indian, and 6 (7.5%) and 29 (8.5%) were unknown.

Smoking status and comorbidities were also observed among patients in the study. In patients from the high-grade immune-related side effects cohort who did and did not experience high-grade immune-related side effects, respectively, 3 (3.8%) and 13 (3.8%) patients were current smokers, 18 (22.5%) and 115 (33.5%) were former smokers, 58 (72.5%) and 215 (62.7%) were never smokers, and 1 (1.3%) and 0 (0%) were unknown. Autoimmune disease was reported in 8 (10.0%) and 27 (7.9%), diabetes mellitus in 12 (15.0%) and 35 (10.2%), hypertension in 22 (27.7%) and 97 (28.3%), hyperlipidemia in 10 (12.5%) and 56 (16.3%), CKD in 7 (8.8%) and 6 (1.7%), preexisting lung disease 32 (40.0%) and 105 (30.6%) and coronary artery disease in 5 (6.3%) and 9 (2.6%).

"Univariate analysis showed that patients [who are White] … were at higher risk of any-grade [immune-related side effects], while older patients, never smokers, and those with chronic kidney disease were at higher risk of high-grade [immune-related side effects]," LeVee and colleagues wrote on the poster.

The most common types of any-grade immune-related side effects included thyroiditis (inflamed thyroid gland; 112 patients), rash (106 patients), colitis (inflamed large intestine; 67 patients), hepatitis (inflamed liver; 49 patients), adrenal insufficiency/hypophysitis (inflamed pituitary glad; 35 patients), arthralgia (joint pain; 25 patients), pneumonitis (inflamed lungs; 11 patients) and diabetes mellitus (eight patients). The majority of these immune-related side effects were grades 1 or 2 (mild or serious).

"Further research is necessary to identify risk factors and biomarkers of immune-related side effectin patients with early breast cancer to help prevent immune-related side effectand mitigate long-term complications," LeVee and colleagues concluded.

References:

"Incidence and Risk Factors of Immune-Related Adverse Events in Early-Stage Breast Cancer Patients: Findings from a Multi-Institutional Study" by Dr. Alexis LeVee, et al. Presented at: 2024 San Antonio Breast Cancer Symposium; December 10-13, 2024; San Antonio, TX. Abstract PS5-03.

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