Breast Cancer and the Role of Clinical Trials

October is Breast Cancer Awareness Month, and this topic hits close to home for me. I’ve spent over six years researching this disease, including working on a clinical trial focused on HER2+ breast cancer. On a personal level, it’s even more profound—my grandmother and several close friends have fought this type of cancer, making this cause incredibly close to my heart.

Nearly 21,000 Australians are expected to be diagnosed with breast cancer in 2024—that’s 58 people every single day. It’s the most common cancer among Australian women, with 1 in 7 receiving a diagnosis at some point in their lives. Globally, breast cancer is also the second most common cause of death for women, with millions of new cases every year. In 2022, approximately 2.3 million new cases of breast cancer were diagnosed globally. Some well-known cases include Christina Applegate, who was diagnosed in 2008, Australian icons Olivia Newton-John and Kylie Minogue, both received their diagnoses in 1992 and 2005, respectively.

While we’ve made tremendous strides in understanding and treating breast cancer, it remains a complex disease with multiple subtypes, each requiring different therapeutic approaches. In this article, I’ll dive into the different types of breast cancer, explore the latest treatment options, discuss ways to reduce risk, and highlight how clinical trials play a crucial role in advancing care and improving outcomes for patients worldwide.

Are You at Risk of having Breast Cancer?

Breast cancer risk is significantly influenced by age and gender, with women being the most affected group. In Australia, the rate of breast cancer diagnoses begins to rise significantly around age 30, with about 25.6 cases for every 100,000 women in that age group in 2014 (see Figure below). The risk rises as women get older, peaking around age 75. For example, women who are 50 years old have a tenfold higher risk of being diagnosed with breast cancer compared to those who are 30. Additionally, in the United States, women under 65 are roughly 5.8 times less likely to develop breast cancer than women aged 65 and older. Together, these reflect the role of hormones on breast cancer.

In addition to age and gender, several factors can increase the risk of breast cancer. These include breast size, family history or genetics, breastfeeding practices, geographic location, and lifestyle choices such as diet, smoking, physical activity, and stress levels. Understanding these risk factors is crucial for better awareness and prevention strategies. For more information on breast cancer risk factors, you can explore resources from the Breast Cancer Network Australia, the American Cancer Society, the National Breast Cancer Foundation, and Cancer Australia.

Breast Cancer Incidence in Australia by Age Group (2017)

This data outlines the age-specific rates of breast cancer diagnoses across different age groups in Australia for the year 2017.

Types of Breast Cancer

Here’s what you need to know about Breast Cancer. It is not a single disease but a group of cancers that originate in the breast tissues. These cancers are classified based on where they start and the presence of certain hormone receptors or proteins.

Invasive Ductal Carcinoma (IDC): The most common type of breast cancer, accounting for about 80% of cases, IDC begins in the ducts (the tubes that carry milk to the nipple) and invades surrounding tissues.
Invasive Lobular Carcinoma (ILC): This type begins in the lobules (the glands that produce milk) and spreads to nearby tissues. It represents around 10-15% of invasive breast cancers.
Ductal Carcinoma In Situ (DCIS): A non-invasive cancer where cells inside the ducts have become cancerous but have not spread outside the ducts. DCIS is highly treatable and is often caught early through mammography.
Triple-Negative Breast Cancer (TNBC): Lacking estrogen receptors, progesterone receptors, and HER2 proteins, TNBC is more aggressive and difficult to treat because it does not respond to hormone therapy. It disproportionately affects younger women, especially those of African descent.
HER2-Positive Breast Cancer: In this type, cancer cells produce too much of the HER2 protein, leading to aggressive growth. However, targeted therapies have significantly improved survival rates for HER2-positive patients.
Inflammatory Breast Cancer (IBC): A rare and aggressive form, IBC blocks lymph vessels in the breast, causing the skin to become red, swollen, and warm. It often progresses rapidly and requires prompt, aggressive treatment.
Male Breast Cancer: Although rare, men can develop this tumour, accounting for about 1% of cases. Men diagnosed with this type of cancer often have IDC, and like women, may carry genetic mutations like BRCA1 or BRCA2.

Breast Cancer Treatment Options

The treatment of breast cancer depends on the type, stage, and specific characteristics of the cancer, such as hormone receptor status and genetic mutations.

Breast cancer is categorized into five main stages based on tumour size, lymph node involvement, and whether it has spread to other organs. Each stage guides treatment and gives insight into prognosis:

Stage 0 (Carcinoma in Situ): Non-invasive; cancer cells are confined within ducts or lobules.
Stage I: Early-stage cancer; tumour ≤2 cm with little to no lymph node involvement.
Stage II: Localized spread; tumour may be 2-5 cm, possibly spreading to nearby lymph nodes.
Stage III: Locally advanced; larger tumours or cancer in multiple lymph nodes, possibly affecting the skin or chest wall.
Stage IV: Metastatic; cancer has spread to distant organs (e.g., lungs, bones, liver).

The TNM system (Tumour, Nodes, Metastasis) further details cancer severity.

Common treatments:

Surgery:
- Lumpectomy: Removes the tumor while preserving most of the breast.
- Mastectomy: Complete removal of one or both breasts.
- Sentinel lymph node biopsy: Removal of one or a few lymph nodes to check if cancer has spread.
Radiation Therapy: Often used after surgery, radiation helps destroy remaining cancer cells in the breast, chest wall, or lymph nodes. It’s especially common after a lumpectomy.
Chemotherapy: Drugs used to kill cancer cells or shrink tumors before surgery (neoadjuvant therapy) or after surgery (adjuvant therapy). It’s also used in advanced cases where cancer has spread.
Hormone Therapy: For cancers that are hormone receptor-positive (ER+ or PR+), treatments like Tamoxifen or aromatase inhibitors are used to block hormones that fuel cancer growth.
Targeted Therapy: Drugs like trastuzumab (Herceptin) and pertuzumab (Perjeta) target HER2-positive breast cancer, dramatically improving outcomes for this aggressive type.
Immunotherapy: Emerging treatments, like pembrolizumab (Keytruda), have shown promise in treating TNBC by helping the immune system attack cancer cells.

Prevention of Breast Cancer

While some risk factors, like genetics, are beyond control, many breast cancer prevention strategies focus on lifestyle changes:

Regular Screening: Mammograms are the most effective early detection tool, particularly for women over 50. Screening aims to detect cancer early when it is more treatable. In Australia, breast cancer screening is primarily managed through the BreastScreen Australia program, which offers free mammograms to women aged 50-74 every two years. Women in this age group receive reminders and are encouraged to participate regularly. While the program primarily targets this age group, women aged 40-49 and 75+ can also access screening if they choose to.
Lifestyle Changes: Maintaining a healthy weight, exercising regularly, limiting alcohol consumption, and eating a balanced diet rich in fruits and vegetables can reduce breast cancer risk. Studies have shown that factors such as reduction in smoking, and weight gain may improve long-term survival of breast cancer patients.
Genetic Testing and Preventive Surgery: Women with a strong family history of this type of cancer may opt for genetic testing to check for mutations like BRCA1 or BRCA2. Some may choose preventive mastectomy or oophorectomy to reduce risk.
Medication: For high-risk women, medications like Tamoxifen or Raloxifene can lower the risk of developing hormone receptor-positive breast cancer.

Breast Changes to Watch For

Finding breast cancer early provides the best chance of surviving the disease. Remember you don’t need to be an expert or use a special technique to check your breasts. Here are some important changes to watch for:

a new lump or thickening, especially if it’s only in one breast
a change in the size or shape of your breast
changes to the nipple, like crusting, sores, redness or it turning inward
nipple discharge that occurs without squeezing
skin changes on your breast such as redness or dimpling
unusual pain that doesn’t go away.

While most of these changes aren’t caused by cancer, it’s important you contact your doctor immediately if you notice anything unusual. Early detection can make all the difference.

The Role of Clinical Trials in Advancing Breast Cancer Treatment

Clinical trials are pivotal in improving health outcomes, from identifying effective treatments to understanding the disease better. Historically, clinical trials have revolutionized treatment options, with key breakthroughs such as:

Tamoxifen Trials (1970s-1990s): Tamoxifen, one of the first hormone therapies for breast cancer, became standard treatment after clinical trials showed it significantly reduced the risk of recurrence in ER+ breast cancer patients.
Herceptin Trials (1990s): The introduction of trastuzumab (Herceptin) for “HER2-positive” breast cancer marked a milestone. Before its discovery, this type of cancer was extremely aggressive with poor survival rates. Clinical trials showed that Herceptin, combined with chemotherapy, improved survival dramatically.
T-DM1 (Kadcyla) Trials (2010s): Trials of this antibody-drug conjugate have provided new hope for patients with HER2-positive breast cancer that has spread or returned after initial treatment.
Immunotherapy for TNBC (2018-Present): Ongoing trials for drugs like pembrolizumab (Keytruda) are exploring how immunotherapy can be used to treat triple-negative breast cancer, which lacks other targeted treatment options. Initial results are promising, with the FDA approving immunotherapy for certain cases of TNBC.
PARP Inhibitors for BRCA-Mutated Cancers: PARP inhibitors like olaparib have shown success in treating breast cancers with BRCA mutations, a breakthrough made possible by clinical trials focused on DNA repair mechanisms.

Current and Future Clinical Trials

Today, clinical trials continue to test new therapies, combinations of existing drugs, and novel approaches like personalized medicine. Some exciting areas of focus include:

Liquid Biopsies: These blood tests detect circulating tumour DNA, potentially allowing earlier diagnosis and monitoring of recurrence without invasive biopsies.
Vaccine Development: Clinical trials are investigating vaccines designed to prevent breast cancer from recurring in high-risk patients by training the immune system to target cancer cells.
Genomic Profiling: Trials are exploring how tumour DNA sequencing can guide more personalized treatments, matching patients with therapies most likely to work for their cancer subtype.

The Path Forward: How We Can Improve

Despite significant progress in cancer treatment, challenges persist, particularly regarding access to care and participation in clinical trials. For instance, Black and Hispanic women experience higher mortality rates largely due to later diagnoses and limited access to innovative treatments. It is essential to address these disparities to improve outcomes for these populations. In order to improve outcomes for all women, we should consider implementing the following strategies:

Increasing Diversity in Clinical Trials: Ensuring that minority groups are adequately represented in clinical trials will help researchers understand how different populations respond to treatment.
Improving Access to Care: Expanding healthcare access, especially in underserved communities, can lead to earlier diagnoses and better treatment outcomes. This is a key focus of our advocacy efforts at Clueo Clinical, as we strive to ensure equitable healthcare for all populations. By addressing barriers to access, we aim to improve health equity and overall patient outcomes.
Expanding Genetic Testing and Counselling: Studies indicate that genetic counselling and testing can lead to significant reductions in cancer incidence among those identified as high-risk, allowing for proactive strategies tailored to their specific needs. Additionally, expanding access can help address disparities in genetic testing uptake, particularly among underserved populations who may not have previously had the opportunity to engage with these vital resources .
Awareness and Education: Continuing public education campaigns, especially during the related Awareness Month, is vital to ensuring that women are aware of the importance of screening and early detection. Studies have shown that awareness campaigns significantly impact women’s likelihood of participating in screening programs. By fostering a culture of prevention and vigilance, these campaigns can contribute to reduced mortality rates and improved health equity among different demographics.

Conclusion

Research has come a long way, but there is still more to be done. Ongoing clinical trials, improved access to clinical trials and care, and addressing disparities in outcomes are essential steps toward a future where breast cancer is not only treatable but preventable. This October, as we honour Breast Cancer Awareness Month, it’s crucial to stay informed, support ongoing research efforts, and advocate for equity in healthcare to ensure better outcomes for everyone affected by this disease.

Dr. Thu (Sue) Nguyen, PhD

Sue is the founder and CEO of Clueo Clinical Pty Ltd. She has over 17 years of combined experience in clinical and pre-clinical research and development, training and management. She is passionate about patient-centric science, clinical research, education, and helping others find their career passion and succeed in life.
She is an avid learner, an authentic networker and wants to empower the next generation to reach their fullest potential in Australia and around the world.