Trastuzumab-Related Heart Problems

Trastuzumab (Herceptin) is an effective treatment for HER2-positive breast cancer. But it can cause serious heart problems. And sometimes, people have to stop taking trastuzumab because of these heart issues.

The MANTICORE trial looked at whether giving standard heart failure medicines while a person is taking trastuzumab, but before any heart problems appear, would prevent those heart problems from ever happening. Researchers found these medicines prevented low left ventricular ejection fraction (LVEF), a way to measure how well your heart is pumping blood. Low LVEF can indicate serious heart problems. By stopping LVEF from getting too low, the heart failure medicines prevented some people from stopping therapy because of heart issues. The researchers say there is practice-changing potential here, but that more study is needed.

Though they helped prevent low LVEF, these medicines did not have a statistically significant effect on another serious effect of trastuzumab, congestive heart failure, or weakness of the heart muscle.

Chemotherapy

Less Chemotherapy?

Breast cancer that is hormone receptor-positive and HER2-negative is considered luminal A. It is a very common subtype, and tends to have a good prognosis. Researchers on the DBCG77B trial wondered if people with this subtype benefit from adjuvant chemotherapy, chemotherapy given after surgery, or not.

They found that in premenopausal women – those not yet in menopause – the rates of cancer coming back in a distant site within 10 years of treatment were similar whether they had adjuvant chemotherapy or not. This suggests that premenopausal women with luminal A breast cancer may be able to avoid chemotherapy, and its side effects, without increased risk of recurrence.

More Chemotherapy?

Breast cancer treatments are sometimes given before surgery, called neoadjuvant therapy, with the hope of shrinking the tumor, or even causing it to disappear.

Researchers with the CREATE-X trial looked at people with early-stage, HER2-negative breast cancer who still had cancer remaining after completing neoadjuvant therapy. After surgery was done, they gave some of these participants capecitabine (Xeloda), a chemotherapy medicine used in metastatic breast cancer.

The researchers found that people who received capecitabine along with standard treatment had a lower risk of the cancer coming back and longer survival than people who received standard treatment alone.

Depends on the Subtype

Carboplatin (Paraplatin) is a member of the platinum family of chemotherapy medicines. In the phase II GeparSixto trial, researchers found that adding carboplatin to standard neoadjuvant chemotherapy greatly improved disease-free survival in people with early-stage, triple-negative breast cancer. But it did not have a similar effect on HER2-positive disease.

The researchers say their study supports using carboplatin as neoadjuvant treatment in people with all stages of triple-negative breast cancer.

Bone-Strengthening Medicine

Aromatase inhibitors, AIs, are a type of hormonal therapy. They can significantly lower the risk of recurrence in women with hormone receptor-positive, early-stage breast cancer who have already started menopause.

But these medicines can also be hard on the bones. For this reason, medicines called bisphosphonates are often given along with AIs to help prevent bone problems. Some research also suggests bisphosphonates may help lengthen the time without disease growth or spread, and overall survival.

Bisphosphonates can have serious side effects. So in the phase III ABCSG-18 trial, researchers looked at a different kind of bone-strengthening medicine, called denosumab (Prolia). Denosumab is a RANK ligand inhibitor.

They found that denosumab strengthened the bones and lengthened the time until disease progression without causing serious side effects. The researchers say denosumab should be offered to all women on AIs.

Circulating Tumor Cells

Sometimes cells break away from tumors and travel through the bloodstream. These are called circulating tumor cells (CTCs). The presence of CTCs soon after chemotherapy ends is associated with lower survival.

Researchers with the phase III Success A trial looked at whether the presence of CTCs two years after chemotherapy treatment for high-risk, early-stage breast cancer would also be associated with lower survival. They found that it was. The researchers suggest that testing for CTCs at follow-up appointments could help doctors identify people who are likely to see the cancer return.

A Decade of Trastuzumab Follow-Up

Today, practically everyone diagnosed with HER2-positive breast cancer receives treatment with the targeted therapy trastuzumab (Herceptin). But that hasn’t been true for very long – trastuzumab has only been FDA approved for use in early-stage disease since 2006.

A decade of follow-up data is now available from BCIRG-006, the study that led to trastuzumab’s approval. That data was presented by the study’s lead investigator, Dennis J. Slamon, MD, PhD. It shows that, compared to treatment with chemotherapy alone, treatment with chemotherapy and trastuzumab leads to significantly longer disease-free survival. This is true even 10 years after treatment has ended.

The data also confirms that trastuzumab works just as well when given with the chemotherapy medicine docetaxel, following treatment with the chemotherapy medicines doxorubicin plus cyclophosphamide, as when it’s given with docetaxel and the chemotherapy medicine carboplatin. It also confirmed that fewer heart side effects are seen with the docetaxel, carboplatin and trastuzumab combination.

Hormonal Therapies for DCIS

Two studies presented on Friday compared the hormonal therapy tamoxifen and an aromatase inhibitor, AI,  in postmenopausal women with ductal carcinoma in situ (DCIS), also known as stage 0 breast cancer.

The first, called the IBIS-II DCIS trial, involved women with hormone receptor-positive DCIS that had been removed by surgery. They were assigned to receive 5 years of tamoxifen or 5 years of the AI anastrozole (Arimidex). Researchers looked at how likely each group of women was to have the breast cancer come back in the breast, called local recurrence, nearby the breast as a regional recurrence, or to develop new breast cancer in the opposite breast.

They found that after a median 7 years, women who had tamoxifen and women who had anastrozole both had about 7 percent less risk of these types of recurrence. There was a difference in side effects though. In the group that had tamoxifen there was a higher risk of uterine cancer and blood clots, while there was some evidence that the AI may reduce the risk of uterine and ovarian cancers.

The second study, called NSABP B-35, also divided postmenopausal women with hormone receptor-positive DCIS into a group that received 5 years of tamoxifen and a group that received 5 years of the AI anastrozole. All women in this study had lumpectomy and radiation therapy. The information presented by lead investigator Patricia Ganz, MD, focused on how symptoms and quality of life differed between the two groups.

The women reported experiencing similar quality of life, regardless of which treatment they received. Side effects were different between the two groups though, with tamoxifen causing more hot flashes and anastrozole causing more joint issues and more vaginal problems, such as dryness and pain during sex. In both treatment groups, women under 60 experienced more menopausal symptoms than women over 60.

Dr. Ganz referred to these types of studies as prevention trials, rather than treatment trials, because they are seeking to prevent future invasive breast cancers. She also noted, after a question from an audience member, that women with DCIS may decide that neither type of hormonal therapy is right for them. They may feel that the benefits don’t outweigh the risks and the side effects. But, she said, it’s important that women have as many facts as possible when they’re making that decision.