Understanding BRCA2, Hormone Receptors, and HER2 in a Second Breast Cancer Diagnosis

For those that know me, you are aware that I received the devastating news that my breast cancer came back. A second breast cancer diagnosis brings a whirlwind of emotions and questions, especially when terms like BRCA2, estrogen-positive, progesterone-positive, and HER2-positive are thrown into the mix. I know many of my family and friends are trying to understand what all of this means, so I thought I’d dive into it in detail more.

What is the BRCA2 Gene?

The BRCA2 gene (Breast Cancer Gene 2) is responsible for producing proteins that help repair damaged DNA. When someone has a BRCA2 mutation, their cells have a harder time repairing DNA damage, increasing their risk for breast, ovarian, pancreatic, and other cancers.

Here’s a breakdown of what BRCA2 means:

• B – Breast: This gene is closely associated with breast cancer risk, although it also increases the risk of ovarian, pancreatic, prostate, and other cancers.
• R – Cancer: Mutations in this gene lead to a higher cancer risk, especially in tissues that rely on BRCA2 for proper DNA repair.
• A – Associated: The gene is linked to hereditary cancer syndromes.
• 2 – This is the second gene identified in the BRCA family after BRCA1. While both genes increase cancer risk, they have some differences in how they function and affect different cancers.

Function of BRCA2

The BRCA2 gene is responsible for producing a protein that helps repair damaged DNA. This process is called homologous recombination repair (HRR), which prevents cells from developing harmful mutations that can lead to cancer.

If someone inherits a BRCA2 mutation, their body’s ability to repair DNA is weakened. This leads to DNA damage accumulating over time, which increases the risk of developing cancer—especially breast and ovarian cancer.

What Does a BRCA2 Mutation Mean?

• Higher Cancer Risk: Women with a BRCA2 mutation have up to a 69% lifetime risk of breast cancer and up to a 20% risk of ovarian cancer. Men also have an increased risk of breast and prostate cancer.
• More Aggressive Cancers: BRCA2-related cancers may develop earlier in life and be more aggressive, requiring more intensive treatment.
• Treatment Impact: Those with BRCA2 mutations may benefit from PARP inhibitors (a targeted therapy) and may consider preventive surgeries like mastectomy or oophorectomy to reduce risk.

BRCA2 vs. BRCA1

Both BRCA1 and BRCA2 mutations increase cancer risk, but they differ in their effects:

• BRCA1 is more strongly associated with triple-negative breast cancer (which lacks hormone receptors and HER2).
• BRCA2 is more often linked to hormone receptor-positive breast cancer (which responds to hormone-blocking treatments).

In short, BRCA2 is a crucial gene for repairing DNA, and when it’s mutated, it greatly increases cancer risk.Understanding this can help individuals make informed decisions about screening, prevention, and treatment.

For those diagnosed with breast cancer once, having a BRCA2 mutation increases the likelihood of a second diagnosis or recurrence. This is because the mutation prevents cells from properly repairing themselves, leading to unchecked growth.

Patients with a BRCA2 mutation often face more aggressive treatment recommendations, such as:

• Double mastectomy (if not already done) to reduce future recurrence risk.
• Oophorectomy (removal of ovaries) to lower estrogen levels, which can fuel certain breast cancers.
• Targeted therapies like PARP inhibitors (e.g., Olaparib) to specifically attack cancer cells with BRCA mutations.

What Does Estrogen and Progesterone Receptor-Positive Mean?

When a breast cancer diagnosis is estrogen receptor-positive (ER+) and/or progesterone receptor-positive (PR+), it means that hormones like estrogen and progesterone are fueling the cancer’s growth.

This is important because it makes the cancer treatable with hormone-blocking therapies, such as:

• Tamoxifen (for premenopausal women)
• Aromatase inhibitors (e.g., Anastrozole, Letrozole, Exemestane) (for postmenopausal women)
• Ovarian suppression (e.g., Lupron) to stop hormone production in premenopausal women

Hormone-positive breast cancers tend to have a better prognosis because they can be treated long-term with these hormone therapies to prevent recurrence.

What Does HER2-Positive Mean?

HER2 (Human Epidermal Growth Factor Receptor 2) is a protein that promotes cancer cell growth. If breast cancer is HER2-positive, it means the cells are producing too much of this protein, leading to faster-growing cancer.

HER2-positive breast cancers used to be more aggressive, but thanks to targeted treatments, outcomes have greatly improved. Common HER2-targeted therapies include:

• Herceptin (Trastuzumab)
• Perjeta (Pertuzumab)
• Kadcyla (T-DM1)
• Enhertu (Trastuzumab deruxtecan)

If someone is HER2-negative, these treatments aren’t needed, and chemotherapy or hormone therapy is used instead.

Treatment Plan for a Second Breast Cancer Diagnosis

A second breast cancer diagnosis can be treated differently depending on these factors:

• BRCA2 mutation → May lead to surgery-based prevention and targeted therapy (PARP inhibitors).
• Hormone Receptor-Positive (ER+/PR+) → Will likely include long-term hormone therapy.
• HER2-Positive → Requires HER2-targeted treatments like Herceptin.

Treatment typically includes:

1. Surgery – Lumpectomy or mastectomy, especially if a BRCA2 mutation is present.
2. Chemotherapy – If the cancer is aggressive, HER2-positive, or hormone-negative.
3. Radiation Therapy – If there is a risk of local recurrence.
4. Targeted Therapy – HER2-targeted drugs or PARP inhibitors for BRCA2 carriers.
5. Hormone Therapy – If the cancer is ER+/PR+, hormone blockers will be prescribed for 5-10 years.

A second breast cancer diagnosis has been daunting, but I have worked hard to understand the BRCA2 gene, hormone receptor status, and HER2. Understand these can help patients and their doctors create a targeted and effective treatment plan. Advances in targeted therapy, surgery, and personalized medicine have made even aggressive breast cancers highly treatable, offering hope for long-term survival.

If you or a loved one are navigating a second diagnosis, like me, lean on your medical team, support system, and available resources to help guide you through this journey.