Removing the Entire Breast Is Not Essential in Multisite Breast Cancer

A new study shows that breast-conserving surgery is appropriate for women with more than one focus of breast cancer and that they have a high likelihood of recovery after this treatment without facing a high risk.

What Is Multisite Breast Cancer?

Breast cancer described as “multicentric” or “multisite” means that tumors are present in more than one breast region, particularly within the same breast. If multisite breast cancer is identified at diagnosis, it is taken into account in treatment planning.

Today, many oncologists or surgeons recommend mastectomy, the removal of the entire breast, for multisite breast cancer even at an early stage. The study discussed here therefore addresses an important oncology question.

An Important Study

The ACOSOG-Z11102 study involved more than 200 women with multiple tumor foci in one breast, predominantly with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer.

After assessment of whether cancer had spread to the axillary lymph nodes, all patients underwent lumpectomy (breast-conserving surgery) and whole-breast radiotherapy, followed by systemic treatment from their oncologist.

After 5 years of follow-up, only 3% of patients had cancer recurrence in the breast.

Although the numbers are small, the data show that, in women with hormone receptor-positive breast cancer, adjuvant (postsurgical preventive) hormone-suppressing therapy substantially reduces the risk of cancer recurrence .

These recent findings were presented on December 9, 2022 at the San Antonio Breast Cancer Symposium (SABCS).

This study provides important information for doctors to discuss with patients who have two or three breast cancer foci in one breast, because it may help more patients consider breast conservation as an option.

In general, lumpectomy plus radiotherapy is now preferred over mastectomy, which removes the entire breast, because it is a smaller operation with faster recovery, leading to greater patient satisfaction and better cosmetic outcomes.

A Study With Eagerly Awaited Results

We knew that lymphadenectomy and mastectomy had the same outcomes in patients with a single tumor in one breast. However, until now, no clinical study of this scope had been designed to test breast-conserving surgery in patients with multisite breast cancer.

Study Details

Diagnoses of multiple cancer foci in the same breast have increased in recent years because diagnostic oncological imaging, such as magnetic resonance imaging (MRI) and PET-CT, is being used more often.

Although older observational studies recorded high local recurrence rates with breast-conserving treatment in women with multisite breast cancer, newer analyses had shown that this approach was associated with “acceptable” recurrence rates.

To examine the safety of breast-conserving treatment in these patients, the team conducted a single-arm phase 2 study in women aged at least 40 with two or three tumor foci in one breast.

The investigators said they knew that a randomized clinical trial design would provide stronger data, but many patients and surgeons were unwilling to accept randomization, so they did not insist on such a design.

Participants were selected such that tumor foci were separated by at least 2 cm of normal tissue and involved no more than two breast quadrants. Patients with early-stage breast cancer were included; there was no lymph node spread, or disease was no more advanced than N1.

Women were excluded if they had tumor foci > 5 cm on imaging, bilateral breast cancer, known BRCA1/2 mutations, a history of unilateral breast cancer or previous neoadjuvant treatment.

All women underwent nodal staging and lumpectomy, with adjuvant chemotherapy at the physician’s discretion, followed by whole-breast irradiation and regional nodal irradiation at the physician’s discretion. This was followed by systemic therapy at the medical oncologist’s discretion.

The women were followed every 6 months for 5 years after completing whole-breast irradiation.

Detailed Results

The primary outcome sought in the study was a local cancer recurrence rate below 8% at 5 years.

• A total of 204 women, with a median age of 61, were assessed in the current analysis.
• Just over half (59.3%) had T1 disease, and 95.6% were lymph node-negative.
• Most (83.5%) had hormone receptor-positive/HER2-negative breast cancer, while 5% had triple-negative tumors and 11.5% had HER2-positive tumors.
• Adjuvant chemotherapy was given to 28.9% of women, and 89.7% of those with hormone receptor-positive disease received adjuvant endocrine therapy.
• The 5-year cancer recurrence rate was only 3.1% (95% CI, 1.3% - 6.4%), well below the predefined “clinically meaningful threshold.”
• There were 4 patients with cancer recurrence in the same breast: one had recurrence in the skin of that breast and one in the chest wall on the same side.
• In addition to the 6 women with local cancer recurrence, 6 had recurrence in the opposite breast and 4 developed distant metastases.
• A total of eight women died during follow-up, but only one death was related to breast cancer.
• An additional analysis showed numerical but nonsignificant associations between local recurrence and pathological stage T2-3 disease, pathological nodal involvement and close surgical margins.
• The 5-year recurrence rate in the 10 triple-negative breast cancer cases was 10%, compared with 2.6% among hormone receptor-positive/HER2-negative patients.
• The team then analyzed adjuvant endocrine therapy in 195 women with at least one positive hormone receptor. It was associated with a 5-year recurrence rate of 1.9%, compared with 12.5% without endocrine therapy. Not receiving adjuvant hormone suppression increased recurrence risk 7.7-fold.

In conclusion, the study showed that breast-conserving surgery is appropriate and sufficient for women with early-stage, hormone receptor-positive/HER2-negative breast cancer and multiple cancer foci in one breast.