Breast Cancer Detected in Breast Milk Earlier Than in Plasma

Researchers say they have detected breast cancer in circulating tumor DNA (ctDNA) from breast milk, and breast milk may allow for earlier cancer detection than plasma.

These results “open up the potential” to use breast milk as a new source for liquid biopsy for breast cancer detection, according to the researchers. They reported their findings in Cancer Discovery.

This study included 19 patients with breast cancer and 12 control individuals without cancer. The researchers collected breast milk samples from the healthy individuals and synchronous tumor biopsies, blood, and breast milk samples from the breast cancer patients.

The breast cancer group included 10 women who were diagnosed during pregnancy and 9 who were diagnosed during the postpartum period while breast feeding. Most (74%) had stage I or II breast cancer.

Four breast cancer patients were ultimately excluded, so the evaluable cohort included 15 breast cancer patients and 12 control individuals.

In the evaluable cohort, the total cell-free DNA (cfDNA) concentration extracted from breast milk in both breasts was, on average, about 90-fold higher than the concentration of cfDNA from blood — 751.7 ng/mL and 8.3 ng/mL, respectively (P <.0001).

There was no significant difference in the concentration of cfDNA extracted from patients with breast cancer and healthy control individuals, or between affected or unaffected breasts.

To determine if ctDNA was present in breast milk, the researchers tested paired samples of breast milk from both breasts and plasma by droplet digital polymerase chain reaction (ddPCR) in 13 of the 15 breast cancer patients. (Two patients did not have synchronous blood samples.)

The researchers identified ctDNA in the affected breast of the 13 evaluable breast cancer patients, and no ctDNA was detected in breast milk from the unaffected breast.

The researchers noted that mutant allele fraction (MAF) levels in breast milk were not significantly associated with markers of disease burden, such as tumor size, stage, nodal status, or disease progression.

However, the percentage of MAF in breast milk varied by maturation stage. Breast milk samples collected in the first 14 days of lactancy had significantly lower variant frequencies than samples collected after 14 days (median, 0.25 and 1.7, respectively; P =.0059).

In addition, the MAF percentage in breast milk was significantly lower in patients with invasive lobular carcinoma than in those with invasive ductal carcinoma (median, 1.0 and 15.0, respectively; P =.0044).

To expand upon the results seen with ddPCR, the researchers used a custom-designed next-generation sequencing panel to evaluate cfDNA from the breast cancer and control groups. The panel targets 54 genes that are often mutated in young patients with breast cancer.

The researchers found that at least 1 genetic variant that was present in tumor tissue was present in 71.4% of breast milk samples. More than 1 variant was found in 42.9% of samples.

The researchers also reported on 2 patients who had frozen breast milk samples from a prior pregnancy. In one case, the sample was collected 18 months before the breast cancer diagnosis, yet the same variant (a PIK3CA p.E545K mutation) was detected in the breast milk sample and in the tumor at diagnosis.

In another case, a patient underwent breast ultrasounds at 8 months, 11 months, and 17 months after childbirth. The patient’s tumor was identified at 17 months. An AKT1:p.E17K clonal variant was found in the tumor tissue and in the breast milk ctDNA at the earlier time points.

“We demonstrate that BM [breast milk] is a superior source of ctDNA as compared with plasma in early-stage breast cancer and could be adapted for early cancer detection in a setting compatible with routine clinical practice,” the researchers concluded.

Disclosures: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Saura C, Ortiz C, Matito J, et al. Early-stage breast cancer detection in breast milk. Cancer Discov. 2023;13:1-12. doi:10.1158/2159-8290.CD-22-1340

This article originally appeared on Cancer Therapy Advisor