Finding and Preparing for Bilateral Breast Cancer Clinical Trials

Calendar Icon July 13, 2021
Reading Time Icon Read Time: 5 min
By Ciitizen

In the past, patients with cancer in both breasts, known as bilateral breast cancer (BBC), often had difficulty locating clinical trials. Unfortunately, they were often routinely excluded, as were patients with metastatic disease, heavily pretreated disease, and/or common comorbidities.

Overcoming Barriers Regarding Availability of Bilateral Breast Cancer Clinical Trials

Over the last several years, there has been a growing interest within clinical, research, and advocate communities to minimize exclusion of those with metastatic breast cancer (MBC), BBC, and frequent morbidities. They emphasize that overcoming such barriers is critical to achieve the following:

  • To effectively study MBCs that behave differently biologically compared with early-stage cancers in tumor growth, spread, and response to specific treatment interventions
  • To increase the participation of advanced breast cancer patients who are highly motivated to participate in clinical trials due to decreased current treatment options
  • To increase the development of unique clinical trial designs based on genetic and molecular alterations
  • To increase the “real-world” applicability of clinical trial safety and efficacy results to the general public with common comorbidities

Searching for Bilateral Breast Cancer Clinical Trials Online

Ten or fifteen years ago, if you visited websites that enabled you to search for clinical trials, searching “bilateral breast cancer” may have resulted in multiple false hits. You may have initially been encouraged by the number of results, only to find that “bilateral breast cancer” was listed in the exclusion criteria rather than the inclusion criteria for specific trials.

However, today, if you conduct that same simple keyword search at ClinicalTrials.gov or other available online cancer search engines, you’ll almost certainly find multiple trials that are active or currently recruiting in which the inclusion criteria specifically includes BBC patients.

You should also proactively ask your oncologist and healthcare team members about whether BBC trials are available where you may be a good fit.

Understanding the Terminology to Effectively Locate Bilateral Breast Cancer Clinical Trials

The incidence of BBC is relatively rare, representing approximately 3% of breast cancer (BC). Since BBC may be described with differing terminology in the medical literature and clinical trial search tools, it’s important to know and use these different terms to effectively search for and locate appropriate clinical trials.

BBCs may be described as the following:

  • Synchronous, indicating that the BC is essentially diagnosed simultaneously in both breasts in the same patient (the cut-off range for BCs described as synchronous is most frequently between three to six months)
  • Metachronous, meaning cases where the second primary breast tumor is diagnosed more than six months after the initial primary tumor diagnosis
  • First and second primary BCs
  • Contralateral BC, meaning a cancer in the opposite breast diagnosed three to six months (synchronous) or more than six months (metachronous) after detection of the first primary BC

Of the 3% diagnosed BBCs, approximately 0.6% are considered synchronous and 2.2% are identified as metachronous tumors. With increased early detection, the diagnosis of BBCs appears to be increasing.

Challenges Inherent to Bilateral Breast Cancer Treatment Decisions

BBC development may be due to genetic predisposition, specific environmental risk factors, and/or unrelated sporadic events. For example, research has found an increased incidence of BBCs in women who received mantle field radiotherapy for Hodgkin’s lymphoma as adolescents and young adults.

For young BC patients, the relative risk of developing metachronous BBC in the opposite breast is high. Those with a history of BC have about a five times higher risk of developing a contralateral primary BC than unaffected people.

As a result, if young patients have developed a secondary primary in the contralateral breast—particularly if they have a family history of BC—genetic testing (e.g., to identify BRCA1, BRCA2, and other mutations known to increase the risk for BC) should be conducted before beginning treatment. Such results could impact optimal therapeutic treatment decisions and may also increase the possibility of clinical trial participation based on inclusion and exclusion criteria.

Should Two Primary Breast Tumors Be Treated as One or Two Diseases?

Determining the standard of care for BC now includes establishing BC stage, grade, and biomarker results, such as those indicating that estrogen receptors (ER), progesterone receptors (PR), and/or HER2 proteins are present and promoting cancer growth. It’s now understood that BC is not a single disease, but rather several complex BC subtypes with different clinical, therapeutic, and prognostic features. Biomarker testing and genomic sequencing to evaluate the genetic makeup of cancer cells are crucial to determining optimal therapeutic strategies.

Should Treatment Be Based on the First Primary Breast Cancer’s Molecular Testing Results?

For patients with BBC, research has suggested that the relative consistency (known as “concordance rates”) of biological markers found in the initial and subsequent BC primary tumors range from approximately 80% to 100%. Such research suggests that similar treatment management—including the use of estrogen-receptor inhibitors and/or anti-HER2 targeted agents and appropriate chemotherapeutic agents—should be based on the biological marker results for the initial primary tumor.

Should Treatment Be Based on Biomolecular Differences Between the Two Breast Cancers?

Research has also found that a patient’s two primary BCs may have different molecular biomarker results, where in some cases, each breast has responded differently to chemotherapy given before surgery. Thus, determining appropriate treatment for patients with two BCs, each with a different hormonal and biomarker status, can be a difficult clinical challenge.

For example, if one primary BC is invasive ductal carcinoma (IDC) that is ER+, PR+, and HER2-, yet the other is IDC ER-, PR-, and HER2+, it may be unclear whether hormonal therapy should be given as part of treatment. Research has shown that HER2+ tumors may inhibit anti-estrogen therapy with Tamoxifen® or aromatase inhibitors. Yet studies have also demonstrated that treatment with anti-HER2 targeted therapies, such as trastuzumab combined with or provided after chemotherapy, may significantly increase patient survival.

Therefore, current research supports treating the two BCs as individual cancers, with therapy directed at achieving optimal synergy between anti-estrogen treatment, chemotherapy, and HER2-targeted therapies and in some cases, specific immunotherapies and targeted radiation.

For example, for patients with BBC where the tumors have mixed hormonal status (e.g., ER+/PR+/HER2- and ER-, PR-, HER2+ tumors), depending on additional patient factors, optimal therapy may include combination therapy, such as anti-endocrine therapy, chemotherapy, anti-HER2 therapy, appropriate immunotherapy, and radiotherapy that uses targeted techniques to help generate immunologic antitumor effects and attenuate radiation therapy’s efficacy.

This is a critical, ongoing area of research where clinical trials are underway.

Should Diagnostic MRI Be Given to the Contralateral Breast?

Risk assessment data does suggest that diagnostic MRI should be considered for those patients, particularly young people, who have high-risk factors for developing synchronous or metachronous BC and who have chosen bilateral mastectomy via contralateral prophylactic mastectomy. Synchronous or metachronous BCs that are found incidentally without MRI may serve to complicate optimal treatment management.

Determining optimal options for treatment and/or potential involvement in bilateral breast cancer clinical trials must be individualized to you as the patient, depending on your preferences and the biology of both of your BCs.

Why Is It Crucial to Have Your Complete Medical Records?

Arriving at optimal treatment decisions can be complex with any BC, but it can be particularly complicated for patients with BBCs. Therefore, it’s critical that you have your complete medical records readily available, including documentation of your surgical pathology reports, BC type, grade, stage, hormonal and HER2 status, and biomarkers and genomic sequence testing results.

Fortunately, Ciitizen, a unique online platform, can assist in obtaining your complex medical records for you at no cost. Ciitizen also has a free clinical trial matching system, so you can easily locate clinical trials that are appropriate for you and your specific BC.

Ciitizen is a free service that helps patients get more out of their health records. Our platform enables patients to find better treatment options and gives them the opportunity to advance the research for cures.

Ready to get your medical records in order? Get started today!

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