Support Continues for Extending Hormonal Therapy in Early-Stage Hormone Receptor-Positive Breast Cancers

Findings announced at the San Antonio Breast Cancer Symposium offer more evidence that continuing hormonal therapy after five years prevents recurrences.
Breast Cancer News
December 7, 2018
Eric Fitzsimmons

Thursday morning’s presentations at the 2018 San Antonio Breast Cancer Symposium focused on treatments for hormone receptorinfo-icon-positive breast cancers. Three studies looked at how hormonal therapyinfo-icon is given, focusing on how long people with early-stageinfo-icon disease should take hormonal therapy and at what doseinfo-icon. The SOLAR-1 trial looked at a new targeted therapyinfo-icon for people with metastaticinfo-icon breast cancer whose disease has a mutationinfo-icon in the PI3K pathway, which occur in 40 percent of hormone receptor-positive breast cancers.

Meta-Analysis of Extended Hormonal Therapy Shows Longer Is Better, For Some

A meta-analysisinfo-icon isn’t a trial itself, but a look at other studies to get a fuller view of a certain feature or treatment. This meta-analysis, by the Early Breast Cancer Trialists’ Collaborative Group, looked at 22,192 women across 11 randomized trials. All trials tested adding 5 years of hormonal therapyinfo-icon with an aromatase inhibitorinfo-icon to 5 years of hormonal therapy (for a total of 10 years on hormonal therapy) to prevent breast cancer from returning.

The study broke the group into three categories: women who took 5 years of tamoxifeninfo-icon, women who started on tamoxifen and then moved to an aromatase inhibitor, and women who took an aromatase inhibitor from the start.

All groups showed a decrease in the chances of cancer returning, either in the breast or to other parts of the body, in the years after they continued hormonal therapy or stopped. People who took tamoxifen for 5 years had a lower risk of breast cancer returning immediately if they stayed on hormonal therapy compared to people who stopped after 5 years. For people who were on aromatase inhibitors, their risk looked the same in the first 2 years of the study period, whether they stayed on hormonal therapy or not, but starting in the third year women who were still taking an aromatase inhibitor had a lower rate of recurrenceinfo-icon than those who had stopped hormonal therapy.

The researchers also broke out the data by other factors, including if and how many lymphinfo-icon nodes were found to contain breast cancer cells. They found a larger difference in risk for recurrence if more lymph nodes were found with cancer. Women who had no nodes with cancer cells had a very similar – and low – risk, whether they stayed on hormonal therapy or not. For women with four or more lymph nodes with cancer cells, the chances of cancer coming back went from 12.2 percent if they continued hormonal therapy to 19.9 percent if they did not.

Researchers continue to consider the question of how long women should take hormonal therapy. This study showed a wide benefit to staying on hormonal therapy, but ongoing research may identify different groups who either benefit from the extended treatment or not. Part of that was captured here, with different treatment histories showing different patterns of recurrence risk and the effect on risk changing with the number of involved lymph nodes.

Still, more information is needed. The study found more side effects with continued treatment, including higher risk of bone fractures, and long-term data were not yet available from some studies included in the analysis. Those findings will be of interest, since many recurrences of hormone receptorinfo-icon-positive breast cancers occur more than 5 years after primary treatmentinfo-icon.

Continuing Hormonal Therapy With Anastrozole Protects Some from Recurrence

The phase III AERAS trial also looked at the question of extending hormonal therapyinfo-icon after 5 years. Women had finished menopauseinfo-icon and been treated for 5 years with the aromatase inhibitorinfo-icon anastrozoleinfo-icon (Arimidex) or had started tamoxifeninfo-icon and then switched to anastrozole for 2 years. They were then randomized to stop hormonal therapy or continue anastrozole for another 5 years.

At 5 years of follow-up, those on extended therapyinfo-icon were more likely to have gone without cancer returning:

  • 91.9 percent of women taking continued anastrozole did not have cancer return.
  • 84.4 percent of women assigned to stop hormonal therapy did not have cancer return.

As in the meta-analysisinfo-icon, continuing treatment came with ongoing side effects, including more bone fractures and more reports of joint paininfo-icon. In the question-and-answer session, some doctors raised concerns that the population of trial participants was too selective, because the women had all been postmenopausalinfo-icon since the start of hormonal therapy and the average body mass indexinfo-icon was lower than expected.

AERAS was not able to show an effect on overall survival. But more positive results for extended therapy continue to help define which women may reduce the chance of cancer returning by extending hormonal therapy. Your doctor can help you weigh the risks against the benefits of continuing hormonal therapy beyond 5 years.

Lower Dose of Tamoxifen Could Become Standard for DCIS, LCIS

One study Thursday looked at giving low doses of tamoxifeninfo-icon to women with Ductal Carcinoma in Situinfo-icon (DCISinfo-icon) or Lobular Carcinoma in Situinfo-icon (LCIS). DCIS and LCIS consist of abnormalinfo-icon cells that have stayed where they first developed. They increase the risk of developing invasive breast cancerinfo-icon later.

After establishing the standard doseinfo-icon for tamoxifen many years ago, the research community has not further studied the smallest dose that can be given to still have an effect. This trial randomized women to a 5 milligram daily dose of tamoxifen or a placeboinfo-icon for 3 years. That dose is significantly less than the standard dose given today of 20 milligrams. The aim was to lower the risk of developing invasive breast cancer while potentially limiting the side effects that can come with the current prescribed dose of tamoxifen.

The study found that the rate of invasive breast cancer incidenceinfo-icon for women taking low-dose tamoxifen was half that of people taking the placebo. Because researchers studied a large group of people for a long time, they measured the rates of invasive disease using person years, which include both the number of people in the study and how long each person spends within it. Over 1,000 people years, 11.6 of those taking tamoxifen were diagnosed with invasive breast cancer, versus 23.9 of those taking the placebo.

Researchers said these findings could be put into practice right away, though the prescriptioninfo-icon would have to be for 10 milligrams every other day because tamoxifen is not made today as a 5 milligram capsule. Finding this protective effect with a smaller dose of tamoxifen could spur on further study as researchers look more for the right level of treatment for different groups. That means giving more treatment to people who need it but giving less treatment to people who don’t get further benefit from it.

SOLAR-1 Trial of Alpelisib Could Bring New Treatment Option in Metastatic Breast Cancer

Researchers gave results from an analysis of the SOLAR-1 trial, which looked at a new targeted therapyinfo-icon called alpelisib added to fulvestrantinfo-icon (Faslodexinfo-icon). Alpelisib is being studied in people with metastaticinfo-icon hormone receptorinfo-icon-positive breast cancer that tests positive for a mutationinfo-icon in the PIK3CA geneinfo-icon. It is not yet FDAinfo-icon approved, but initial promising results were announced in October at the European Society for Medical Oncologyinfo-icon annual congress.

Alpelisib is a PI3K (phosphatidylinositol-3 kinase) inhibitor, meaning it blocks the PI3K pathway through which signals are carried through cancer cells. This pathway is thought to be involved in breast cancers becoming resistant to hormonal therapyinfo-icon. About 40 percent of hormone receptor-positive breast cancers have a mutation on the PIK3CA gene that makes this pathway hyperactive.

The study was open to men or postmenopausalinfo-icon women with hormone receptor-positive, HER2-negative breast cancer. Everyone had their disease grow within a year of finishing treatment for early-stage breast cancerinfo-icon or while taking anti-estrogeninfo-icon therapyinfo-icon for metastatic breast cancer. Participants were split into two arms, those with a mutation in the PIK3CA gene and those without. Those groups were split and randomized to get fulvestrant either with a placeboinfo-icon or with alpelisib.

The primary goal of the trial was to measure medianinfo-icon progressioninfo-icon free survival – the time a person goes without cancer growing or traveling to another part of the body – in the arm with a PIK3CA mutation, and this was achieved:

  • People taking alpelisib went 11 months without cancer growing.
  • People taking a placebo went 5.7 months without cancer growing.

A concern with PI3K-inihibitors is high blood sugar or hyperglycemia; the PI3K pathway is involved in the way the body regulates insulin. But researchers said high blood sugar can be easily identified and managed with medicineinfo-icon. Earlier PI3K inhibitors under study had too many side effects, which did not allow them to be further developed.

Overall survival will be watched in future follow-ups, but the positive results today show promise for a potential new treatment option for people with hormone receptor-positive metastatic breast cancer whose cancers have a PIK3CA gene mutation.

Additional Related Topics 
Hormonal Therapy