Research in breast cancer

We are always learning more about cancer. Researchers and healthcare professionals use what they learn from research studies to develop better practices that will help prevent, find and treat breast cancer. They are also looking for ways to improve the quality of life of people with breast cancer.

The following is a selection of recent research showing promise for treating breast cancer.

We’ve included information from the following sources. Each item has an identity number that links to a brief overview (abstract).

• PubMed, US National Library of Medicine (PMID)
• American Society of Clinical Oncology (ASCO)
• Canadian Cancer Trials and ClinicalTrials.gov (NCT)

Researchers are looking for the best ways to treat breast cancer using surgery and to improve surgical techniques.

Axillary (underarm) lymph node surgeries are part of the staging process for breast cancer. Sentinel lymph node biopsy (SLNB) for breast cancer is surgery to find and remove one or a few underarm sentinel lymph nodes to see if they contain cancer cells. Axillary lymph node dissection (ALND) is surgery to remove a greater number of lymph nodes (usually 15 to 20) from the armpit. ALND has a higher risk of causing permanent arm swelling (lymphedema) than SLNB. Until recently, it was standard to perform ALND after SLNB if tumour cells were found in one or more sentinel lymph nodes. In a recent study, researchers compared SLNB alone to ALND in women with breast tumours smaller than 50 mm wide (called T1 and T2) that had spread to only 1 or 2 sentinel lymph nodes who would be treated with lumpectomy followed by radiation therapy. The rates of cancer recurrence in the underarm lymph nodes and overall survival were the same with both types of surgery (JAMA, PMID 28898379). Based on these results, breast surgeons are no longer performing ALND for this group of women.

Breast reconstruction surgery makes the breast look and feel as natural as possible after part or all of it is removed. Immediate reconstruction involves inserting an implant at the same time as mastectomy. Immediate-delayed reconstruction involves inserting a tissue expander at the same time as mastectomy. Doctors slowly inflate the tissue expander by filling it with normal saline (salt water) over several weeks. Then, several months after the mastectomy, additional surgery is done to remove the tissue expander and insert an implant in the tissue “pocket” created by the expander. Immediate reconstruction means that the woman never has to be without a breast and can avoid a second surgery, but it is technically more difficult because the implant does not have a natural tissue pocket to anchor it in place. To try to anchor an implant inserted at the time of mastectomy, plastic surgeons commonly place a collagen (a type of protein) substance called acellular dermal matrix (AlloDerm, DermaMatrix). This matrix is made from donated human skin tissue from which the cells have been removed to prevent rejection. A recent study randomly assigned women to undergo 1 of these 2 ways of doing breast reconstruction surgery. The study showed that immediate reconstruction was linked with complications almost 4 times more often than immediate-delayed reconstruction (Lancet Oncology, PMID 28012977).

Researchers are looking for ways to improve radiation therapy as a treatment for breast cancer.

Radiation therapy to axillary (underarm) lymph nodes may be an alternative to surgery to remove them (called axillary lymph node dissection, or ALND). ALND is usually used to treat women with breast cancer that has spread to at least 1 underarm lymph node, who are treated with chemotherapy followed by breast surgery including a sentinel lymph node biopsy (SLNB) and who still have cancer in at least 1 underarm lymph node. In an ongoing clinical trial, these women are randomized to receive either the standard treatment of ALND or radiation to the axillary lymph nodes. The trial is looking for any differences in the cancer recurrence rate (the length of time before breast cancer comes back) and overall survival between the 2 groups of women. It is also trying to find out if lymphedema develops less often with 1 of the treatments (ClinicalTrials.gov, NCT 01901094). Another study compared radiation therapy to the axillary lymph nodes to ALND for women with a breast tumour no larger than 3 cm in diameter with cancer that had spread to at least 1 sentinel lymph node. Results show that almost 40% of women had cancer in additional lymph nodes at ALND, which implies that a similar number of women in the radiation group had axillary disease. They also show that radiation was at least as good as surgery at preventing recurrence in the axillary lymph nodes (European Journal of Surgical Oncology, PMID 28139362). Radiation also seems to lead to better overall survival.

Radiation therapy to regional lymph nodes may lower the chance that breast cancer will recur. A Canadian study looked at women who had breast cancer in 3 or fewer underarm lymph nodes or who didn’t have cancer in the lymph nodes but had a high risk of recurrence. These women were assigned to 2 groups. One group was given radiation therapy to the whole breast and the regional lymph nodes (lymph nodes in the armpit, along the side of the breast bone and in the lower neck). The other group was given radiation only to the breast. The results of the study show that both groups had the same survival rates after 10 years. But breast cancer recurred less often in women who had radiation to the regional lymph nodes as well as the breast (New England Journal of Medicine, PMID 26200977). The group who received radiation to the regional lymph nodes had significantly more short- and long-term side effects. In another non-randomized study, researchers looked at women with breast cancer that had spread to axillary lymph nodes who underwent ALND and were then treated with adjuvant HER2-targeted therapy, with or without radiation to the regional lymph nodes. After an average follow-up of 4.5 years, the rate of cancer recurrence was similar in women who did and didn’t receive radiation to the regional lymph nodes, after adjusting for other differences between the groups (Journal of the National Cancer Institute, PMID 28376188).

Accelerated partial breast radiation directs radiation only to the area of the tumour in the breast, instead of to the whole breast. It is considered accelerated because the radiation is given in larger doses over a shorter period of time than standard radiation therapy. Studies show that accelerated partial breast radiation has fewer side effects than radiation to the whole breast, but it has the same risk of cancer recurrence in the breast and the same survival rates (European Journal of Cancer, PMID 25605582, PMID 28262584; Lancet Oncology, PMID 28094198).

Radiation after a mastectomy may be given if cancer has spread to the lymph nodes. Recent follow-up studies show that, with today’s current treatments, radiation therapy has little effect on local recurrence and no effect on overall survival when given after mastectomy for women with breast cancer that has spread to 1 to 3 lymph nodes (Radiotherapy and Oncology, PMID 28341062; Surgical Oncology, PMID 28577722).

Breath holding techniques may be used during radiation therapy to reduce the amount of radiation exposure to the heart, especially when the left breast is being treated. One study taught a group of women to hold their breath while having radiation treatment, and then measured the amount of radiation that reached the heart muscle. Researchers compared the amount of radiation received by the heart when women held their breath or breathed normally during the treatment. They found that holding the breath lowered the amount of radiation absorbed by the heart and could help reduce heart damage from radiation therapy (Clinical Oncology, PMID 27890346; Anticancer Research, PMID 28179347).

The following is noteworthy research in chemotherapy for breast cancer.

More women with early breast cancer can safely skip chemotherapy. The TAILORx Breast Cancer Trial showed that 70% of women with early estrogen receptor–positive (ER+) breast cancer that has not spread to the underarm lymph nodes do not benefit from chemotherapy. It used a molecular test called Oncotype DX, which is performed on preserved breast tumour tissue. The test produces a Recurrence Score between 0 and 100, based on the expression of 16 tumour genes. This score predicts the probability that the cancer will come back if hormone therapy with tamoxifen (Nolvadex, Tamofen) is given for 5 years without chemotherapy. The trial found that women with a Recurrence Score of 15 or less have an excellent prognosis with hormone therapy (tamoxifen or an aromatase inhibitor) alone and do not benefit from the addition of chemotherapy. Women with a Recurrence Score of higher than 25 benefit from the addition of chemotherapy. Women younger than age 50 with a score between 16 and 25 (particularly those with a score of 21 to 25) who received chemotherapy in addition to hormone therapy had a lower risk of recurrence than those who received hormone therapy alone (New England Journal of Medicine, PMID 26412349, PMID 29860917; Cancer, PMID 28199747). However, the great majority of these women did not receive hormonal therapy that would be considered optimal today.

Bisphosphonates are drugs that help strengthen bone by stopping the body from breaking it down. A recent review of a large number of studies (called a meta-analysis) showed that bisphosphonates, such as intravenous zoledronic acid (Zometa) or oral clodronate (Bonefos), lower the rate of bone metastases and improve survival in women with early stage breast cancer (The Lancet, PMID 26211824; The Lancet Oncology, PMID 29037984; Cancer, PMID 28464211).

Researchers are looking for better ways to treat hormone receptor–positive breast cancer, especially in premenopausal women (women who are still menstruating).

Hormone therapy with aromatase inhibitors and ovarian suppressors can improve survival for premenopausal women with breast cancer. Ovarian suppressors are drugs (usually injected every 4 weeks) to lower or stop the ovaries from making estrogen. Studies show that premenopausal women who have surgery to remove the ovaries or receive ovarian suppressors in addition to tamoxifen have better disease-free and overall survival compared to those who receive tamoxifen alone. Aromatase is an enzyme that the body uses to make estrogen in areas of the body other than the ovaries. Aromatase inhibitors are drugs that stop the production or block the actions of aromatase, which lowers the level of estrogen in the body. Aromatase inhibitors are only active in premenopausal women if the ovaries are removed or suppressed. Using aromatase inhibitors plus ovarian suppressors instead of tamoxifen plus ovarian suppressors for 5 years further increases disease-free survival and overall survival rates, but it can lead to more side effects from low estrogen levels (New England Journal of Medicine, PMID 29863451).

Researchers are looking at new targeted therapies for treating breast cancer.

Biosimilars are drugs that are chemically similar (but not identical) to an existing biologic agent. They have identical effects on tumour cells as an existing biologic agent. A biologic agent is a substance made from a living organism or its products. In biosimilars, the original biologic agent is a very large protein that does not have a fixed chemical structure. Research shows that the biosimilar CT-P6 is just as effective as trastuzumab (Herceptin) in treating HER2-positive early breast cancer (Lancet Oncology, PMID 28592386; JAMA, PMID 27918780).

Pertuzumab (Perjeta) in addition to trastuzumab improves the effectiveness of breast cancer treatment in women with metastatic disease. Pertuzumab is a monoclonal antibody, like trastuzumab. Researchers are trying to find out if pertuzumab is also effective in treating women with early breast cancer. They found that pertuzumab in addition to trastuzumab and chemotherapy mildly improves disease-free survival in women with HER2-positive breast cancer when it is given after surgery for non-metastatic disease. Although the overall benefit is very small, there is slightly more benefit for women with cancer that has spread to the underarm lymph nodes and for women with estrogen receptor–negative (ER–) breast cancer (New England Journal of Medicine, PMID 28581356).

Olaparib (Lynparza) is an oral poly ADP-ribose polymerase (PARP) inhibitor. PARP is an enzyme that helps repair damage to DNA and is particularly important for cells with a defect in a DNA-repair gene (such as BRCA1 or BRCA2). PARP inhibitors block PARP so cancer cells can’t repair their DNA, which causes them to die. Olaparib provided a significant benefit over standard therapy for HER2-negative metastatic breast cancer in women with a germline BRCA mutation (New England Journal of Medicine, PMID 28578601). Researchers are currently studying olaparib in a randomized trial of women with non-metastatic disease who have a BRCA mutation to find out if 1 year of olaparib given after chemotherapy can decrease recurrence and improve survival (ClinicalTrials.gov,NCT 02032823).

Cyclin-dependent kinases (CDKs) are proteins that control the cell cycle. CDK inhibitors block these proteins to help slow or stop the growth of cancer cells. Randomized trials looked at post-menopausal women with hormone receptor–positive, HER2-negative metastatic breast cancer who have not yet received treatment for metastatic disease. They found that adding the CDK4/6 inhibitors palbociclib, ribociclib or abemaciclib to an aromatase inhibitor significantly increases response rates and duration of response compared to an aromatase inhibitor alone with very few side effects (Journal of Clinical Oncology, PMID 28968163, PMID 28580882; Oncologist, PMID 28652278; New England Journal of Medicine, PMID 27717303). Studies are currently underway to determine if adding a CDK4/6 inhibitor to standard adjuvant hormonal therapy improves disease-free and overall survival in women with high-risk ER+ disease (Clinicaltrials.gov, NCT 02513394).

Researchers continue to try to find out more about breast cancer. Clinical trials are research studies that test new ways to prevent, detect, treat or manage breast cancer. Clinical trials provide information about the safety and effectiveness of new approaches to see if they should become widely available. Most of the standard treatments for breast cancer were first shown to be effective through clinical trials.

Find out more about clinical trials.