In the treatment of breast cancer, most women diagnosed with early stage breast cancer are candidates for breast-conserving surgery with radiotherapy or mastectomy. Numerous studies have shown that the risk of local recurrence and the chance of survival does not differ with these approaches.
Sentinel node biopsy, a procedure in which the sentinel lymph node is identified, removed, and examined to determine whether cancer cells are present, is used for axillary staging. In ongoing treatment, an individualized patient approach is designed to minimize the need for axillary dissection in women with positive sentinel nodes. Based on proven survival benefit, adjuvant systemic therapy is recommended in the majority of patients. To individualize treatment, molecular profiling, based on risk is used for the treatment of patients with hormone receptor-positive cancers.
Breast conserving therapy, which removes the cancer while leaving as much normal breast as possible, is a less invasive type of treatment with fewer side effects. This approach is accepted as a preferred option for unifocal breast cancer. However, the oncologic safety of breast conserving therapy for multiple ipsilateral breast cancer (MIBC), has not been demonstrated in a prospective study.
To assess the local recurrence rate with breast-conservation in patients with multiple ipsilateral primary breast cancer, the American College of Surgeons Oncology Group Alliance (ACOSOG) Z11102 phase II single arm prospective trial (NCT01556243) was designed to evaluate outcomes with breast conserving therapy for multiple ipsilateral breast cancer.
The purpose study was to find out how well breast-conserving surgery and radiation therapy work in treating patients with multiple ipsilateral breast cancer.
The outcome demonstrated that patients with multiple tumors in the same breast who underwent a lumpectomy followed by radiation therapy had local recurrence rates comparable to those historically observed in patients with a single tumor.
This is a conclusion based on data from the prospective phase II clinical study, which was supported by the National Institutes of Health. The results were presented at the San Antonio Breast Cancer Symposium, held December 6-10, 2022.
“Most patients who present with two or three sites of cancer in one breast are recommended to undergo a mastectomy, as historical studies showed high local recurrence rates in patients who underwent breast-conserving therapy consisting of lumpectomy and radiation therapy,” explained Judy C. Boughey, MD, the W.H. Odell Professor of Individualized Medicine and Chair of the Division of Breast and Melanoma Surgical Oncology at the Mayo Clinic.
“Advances in imaging techniques have led to greater detection of additional breast tumors, leading to more patients undergoing mastectomy who otherwise may have preferred breast-conserving therapy,” she added.
“To date, there have been no prospective clinical trials evaluating local recurrence after
breast-conserving therapy for patients with multiple ipsilateral breast lesions. The main purpose of this trial was to evaluate whether lumpectomy followed by radiation therapy was an appropriate management for patients who had more than one tumor in a single breast.”
The trial enrolled women over the age of 40 who had two or three sites of breast cancer (each site < 5cm in size with at least 1 site invasive) inn the same breast separated by >2-3 cm of normal breast tissue and disease limited to two quadrants of the breast with cN0 or cN1 disease. All patients had undergone pre-operative mammogram and/or ultrasound, and most had undergone breast MRI as well. In this study, neoadjuvant therapy was not allowed.
Fourteen of the enrolled patients converted to mastectomy due to persistent positive margins, which precluded breast-conserving therapy.
The remaining patients were treated with lumpectomy resected to negative margins followed by whole breast radiation therapy with radiation boosts to all lumpectomy sites.
In this study, the primary endpoint was local recurrence at five years after the completion of radiation. The cumulative incidence of local recurrence (LR, defined as histologic evidence of ductal carcinoma in situ (DCIS) or invasive breast cancer in the ipsilateral breast or chest wall) at 5 years (treating death and distant and nodal/regional recurrence as competing risks) to assess whether the rate is greater than 8%.
The cut-off for the study data was May 25, 2022
Among the 204 evaluable patients [median age 61 (range 40-87)], six patients developed local recurrence (5 ipsilateral breast and 1 chest wall) after a median follow-up of 66.4 months (range: 4.1, 90.6), for a five-year local recurrence rate of 3.2% ((95% CI: 1.3, 6.4). This rate was similar to the local recurrence rates seen in prior studies for patients with a single breast tumor who underwent breast-conserving therapy.
The rate of local recurrence was greater among the 15 patients who did not undergo a pre-surgical breast MRI compared with the 189 patients who underwent this imaging (22.6% vs. 1.7%). Boughey noted that this may have been due to greater detection of disease sites prior to surgery in patients who underwent breast MRI, potentially allowing for more thorough resection. The risk of local recurrence was not associated with patient age, number of breast lesions, tumor biology, or pathologic staging categories.
Non of the participating patients developed regional recurrence; however, five patients developed distant recurrence, five patients developed breast cancer in the opposite breast (contralateral breast cancer), three patients developed new non-breast primary tumors, and eight patients died (including one death related to breast cancer).
The results if this study demonstrates that for women with multiple ipsilateral breast cancer breast conserving surgery with adjuvant radiation and with lumpectomy site boosts, has an acceptably low local recurrence rate (3.2% at 5 years).
“This study provides important information for clinicians to discuss with patients who have two or three foci of breast cancer in one breast, as it may allow more patients to consider breast-conserving therapy as an option,” said Boughey.
“Lumpectomy with radiation therapy is often preferred to mastectomy as it is a smaller operation with quicker recovery, resulting in better patient satisfaction and cosmetic outcomes.”
Boughey concluded that the results from the trial also suggest that patients who are diagnosed with two or more malignant lesions in the breast and are considering breast-conserving therapy may benefit from breast MRI.
A limitation of the study was its single-arm design. “While a randomized trial design would have provided stronger data, we felt that accrual to such a design would be problematic as many patients and surgeons would not be willing to randomize,” Boughey concluded.
Summary of study data
|Characteristics||Estimated rate of LR at 5 years (95% CI)||# patients with local recurrence||HR (95% CI)||p-value|
|All Patients (n=194)||6|
|Patient age (years)||0.98|
|≤ 60 (n=96)||3.1 (1.1 – 9.7)||3||1.00 (ref)|
|> 60 (n=98)||3.1 (1.1 – 9.7)||3||0.98 (0.20 – 4.85)|
|Bilateral MRI done||0.002|
|Yes (n=180)||1.7 (0.6 – 5.2)||3||1.00 (ref)|
|No (n=14)||22.6 (7.9 – 55.1)||3||13.36 (2.69 – 66.25)|
|Number of biopsy proven sites of breast cancer on work||NE|
|2 (n=185)||3.4 (1.5 – 7.4)||6||NE|
|Negative (n=169)||3.7 (1.7 – 8.0)||6||NE|
|Pathologic T Category||0.12|
|T0/Tis/T1 (n=150)||2.1 (0.7 – 6.3)||3||1.00 (ref)|
|T2/T3 (n=43)||7.4 (2.4 – 21.2)||3||3.59 (0.72 – 17.77)|
|Pathologic N Category||0.11|
|N0 (n=148)||2.1 (0.7 – 6.4)||3||1.00 (ref)|
|N1+ (n=43)||7.6 (2.5 – 21.7)||3||3.68 (0.74 – 18.21|
Breast-Conserving Surgery and Radiation Therapy in Patients With Multiple Ipsilateral Breast Cancer – NCT01556243
 Boughey JC. Impact of Breast Conservation Therapy on Local Recurrence in Patients with Multiple Ipsilateral Breast Cancer – Results from ACOSOG Z11102 (Alliance). Abstract GS4-01 presented during the San Antonio Breast Cancer Symposium, held December 6 – 10, 2022 in San Antonio, Tx.
Featured image: San Antonio Breast Cancer Symposium (SABCS) held December 6 – 10, 2022 at the Henry B. Gonzalez Convention Center in San Antonio, Tx. Photo courtesy: © 2022 AACR/SABCS MedMeetingImages/Todd Buchanan. Used with permission.