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Unlocking Locally Advanced Breast Cancer: the CAPItello-291 Trial

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Introduction to Locally Advanced Breast Cancer

Breast cancer is one of the most common types of cancer diagnosed in women worldwide. It’s a condition that comes in many forms and stages, each with its own set of characteristics, treatment options, and prognoses. One such stage that requires our attention and understanding is locally advanced breast cancer.

The term LABC or locally advanced breast cancer is a term used to describe cancer that is larger in size, generally greater than 5 cm, and may have spread to nearby tissues such as the skin or chest wall, or to lymph nodes within the breast or underarm area.

However, it hasn’t spread to distant organs like the lungs or liver.

According to the American Cancer Society, locally advanced breast cancer usually corresponds to stage III of breast cancer, although some stage II cancers may also be considered locally advanced.

This is a stage that requires a more aggressive approach to treatment compared to early-stage cancers.

Treatment for this type of cancer often involves a combination of systemic therapy like:

Understanding locally advanced breast cancer and how it differs from other stages is critical for patients and their loved ones, as it informs decision-making around treatment strategies and what to expect in terms of outcomes.

Locally Advanced Breast Cancer: Symptoms, Outlook, and More

Understanding the symptoms of locally advanced breast cancer can play a critical role in its early detection and consequently, its management.

The symptoms are not distinct from breast cancer in general; however, their intensity or severity may differ due to the extent of the cancer’s spread.

Symptoms of Locally Advanced Breast Cancer

Typically, the symptoms can include the following:

  1. A lump or thickening in the breast or underarm area that persists after your menstrual cycle. This is often the first noticeable symptom.

  2. Change in the size or shape of the breast.

  3. Dimpling or puckering of the skin.

  4. A nipple turned inward into the breast.

  5. Scaly, red, or swollen skin on the breast, nipple, or areola (the dark area of skin at the center of the breast).

  6. Fluid, other than breast milk, from the nipple, especially if it’s bloody.

It is essential to remember that these symptoms do not definitively diagnose breast cancer, let alone locally advanced breast cancer.

Outlook for Locally Advanced Breast Cancer

The outlook or prognosis for locally advanced breast cancer is largely dependent on various factors, including the specific characteristics of the cancer, the patient’s overall health, and how well the cancer responds to treatment.

The American Cancer Society notes that although this stage is more serious than early-stage breast cancer, many people can still go on to live a normal life span with proper treatment.

Modern advancements in breast cancer treatment options have significantly improved the outlook for locally advanced breast cancer.

According to the National Cancer Institute, systemic therapies like chemotherapy, hormone therapy, targeted therapy, and immunotherapy, coupled with local therapies like surgery and radiation, have improved outcomes.

However, it is important to remember that the prognosis varies significantly from person to person.

Each individual’s journey with breast cancer is unique and depends on a multitude of factors.

Understanding the Prognosis of Locally Advanced Breast Cancer

When discussing breast cancer, the term “prognosis” refers to the expected outcome or course of the disease.

It’s a prediction of the likely progression of the disease, including considerations such as:

Factors Affecting the Prognosis

Different factors can influence the prognosis of locally advanced breast cancer, including but not limited to:

  1. Size of the tumor: larger tumors tend to have a poorer prognosis than smaller ones, as they may suggest a more aggressive or advanced disease.

  2. Lymph node involvement: the presence of cancer cells in the lymph nodes can affect the prognosis. A greater number of affected lymph nodes typically correlates with a more severe prognosis.

  3. Grade of the tumor: the grade of a tumor refers to how much the cancer cells resemble normal cells when viewed under a microscope. Higher grade cancers tend to grow and spread more rapidly than lower grade cancers, leading to a poorer prognosis.

  4. Hormone receptor status: breast cancers that are hormone receptor-positive can be treated with hormone therapies.

  5. HER2 status: breast cancers that overexpress the HER2 protein can be more aggressive, but targeted therapies can effectively treat them.

  6. Patient’s general health: the overall health of the patient can impact how well they respond to treatment.

General Statistics on the Prognosis of Locally Advanced Breast Cancer

According to the American Cancer Society, the five-year relative survival rate for women with Stage III (locally advanced) breast cancer is about 72%.

However, this statistic is an average that encompasses a wide range of individual situations, including varying sub-stages of Stage III breast cancer.

It’s important to note that these survival rates are based on data from people diagnosed several years ago.

Thanks to advances in detection and treatment, the prognosis for people currently diagnosed with locally advanced breast cancer may be more favorable.

If the prognosis can significantly improve with effective and timely treatment. It would mean that it can be faster to understand a diagnosis; knowing what questions to ask, and getting appropriate care are all crucial steps towards better outcomes.

Lastly, prognosis is just a prediction.

Many people with locally advanced breast cancer may live far beyond the times suggested by these statistics, particularly with the help of novel treatment approaches, supportive care, and healthy lifestyle choices.

The Stage of Breast Cancer: Locally Advanced

Understanding the stage of breast cancer is crucial in evaluating the progression of the disease and deciding on the most effective treatment strategy.

The term “locally advanced” generally applies to Stage III and some Stage IV breast cancers.

Staging Breast Cancer

Breast cancer staging is a system used by healthcare professionals to categorize the extent of cancer spread.

According to the American Joint Committee on Cancer (AJCC), it is typically described in stages 0 through IV, with each stage having further subdivisions.

Understanding Stage III – The Locally Advanced Stage

Stage III breast cancer is divided into three subcategories: IIIA, IIIB, and IIIC.

It’s important to note that while Stage III cancer is advanced, it is not the same as metastatic (Stage IV) breast cancer.

Locally advanced breast cancer is still contained within the breast and nearby lymph nodes, while metastatic breast cancer has spread to distant parts of the body.

A Glimpse into Stage IV – Is It Locally Advanced?

Stage IV breast cancer, also known as metastatic breast cancer, is when cancer cells have spread beyond the breast and nearby lymph nodes to other parts of the body such as the lungs, liver, bones, or brain.

It can be diagnosed at the first presentation, or it can be a recurrence of a previous breast cancer that has spread.

While some early Stage IV cases may be classified as locally advanced, it is generally considered a stage beyond, given the distance of cancer spread.

Staging in Context – What Does It Mean for Patients?

The stage of cancer at the time of diagnosis plays a crucial role in determining the course of treatment.

For locally advanced breast cancers (Stage III), treatments typically involve a combination of surgery, radiation therapy, chemotherapy, and targeted therapies or hormone therapy.

Staging provides a common language for patients and their healthcare providers to discuss the disease, but the experience and prognosis can vary greatly from person to person.

The Meaning of Locally Advanced Cancer

Regarding to understand cancer terminology, the phrase “locally advanced” may be a bit perplexing.

Though it sounds severe, grasping its definition and what it implies for the disease’s course and progression is important in understanding the journey ahead.

Defining “Locally Advanced”

Cancer stages range from I to IV, with each stage representing the extent of cancer’s spread.

As we’ve noted, “locally advanced” is a term that generally applies to Stage III and, in some cases, Stage IV breast cancers.

The National Cancer Institute defines locally advanced cancer as cancer that has spread from where it started to nearby lymph nodes or tissues but not to other parts of the body.

For breast cancer, this implies that the cancer cells have moved beyond the original tumor site in the breast tissue but are still confined within the breast or have spread to nearby lymph nodes.

What Does “Locally Advanced” Imply for the Patient?

Being diagnosed with locally advanced breast cancer often means the cancer is larger and has spread more extensively in the breast, chest wall, and/or lymph nodes than early-stage breast cancers.

It indicates a more serious condition that typically requires more aggressive and comprehensive treatment.

This diagnosis can understandably feel overwhelming.

The advent of innovative targeted treatments, along with more traditional approaches, means there are numerous options available to manage locally advanced breast cancer.

Disease Progression: Locally Advanced Vs. Metastatic

The term “locally advanced” distinguishes this stage from metastatic or Stage IV breast cancer, which is when the cancer cells have spread beyond the breast and nearby lymph nodes to distant parts of the body, such as the lungs, liver, bones, or brain.

This difference has significant implications for treatment and prognosis.

While a diagnosis of locally advanced breast cancer is certainly serious, it is important to remember that there are effective treatments available. The advances in breast cancer treatment, particularly for locally advanced disease, have been dramatic.

As noted by the American Cancer Society, survival rates have been improving for decades, and many women with locally advanced breast cancer go on to live long, fulfilling lives.

Advanced Versus Locally Advanced Cancer: Understanding the Difference

Cancer classifications can sometimes seem like a confusing array of medical jargon.

Two terms that are often misinterpreted or interchanged are “advanced” and “locally advanced.”

Understanding these distinctions is critical, as it impacts the course of treatment and the disease’s outlook.

What Does “Advanced Cancer” Mean?

In general terms, advanced cancer is often used interchangeably with Stage IV or metastatic cancer.

Advanced cancer is defined as cancer that has spread from the original (primary) tumor to distant organs or distant lymph nodes.

This means that the cancer cells have moved far beyond the immediate area of the primary tumor site.

For instance, in the context of breast cancer, advanced breast cancer would mean the cancer has spread beyond the breast and nearby lymph nodes to distant areas of the body, like the lungs, liver, bones, or brain.

Unveiling “Locally Advanced Cancer”

On the other hand, as previously discussed, locally advanced cancer is a stage of cancer that is more extensive than the early stages but not as widespread as advanced (metastatic) cancer.

Locally advanced cancer is typically confined to the primary site and possibly nearby lymph nodes.

In breast cancer, locally advanced disease (generally classified as Stage III) implies that the cancer is larger and has spread more extensively within the breast, chest wall, and/or nearby lymph nodes, but it has not yet spread to distant organs.

Why the Distinction Matters

Distinguishing between advanced and locally advanced cancer is crucial for a few reasons.

The stage of cancer at the time of diagnosis guides treatment decisions and helps provide information about prognosis.

Advanced or metastatic cancer typically requires systemic therapy as the main treatment, often for an extended period of time or indefinitely. While locally advanced cancer typically is treated with a combination of local treatments such as surgery and/or radiation therapy, and systemic therapy.

The prognosis of advanced cancer differs substantially from that of locally advanced cancer.

Generally, the prognosis worsens as the cancer stage increases, with metastatic or advanced cancer having a poorer prognosis compared to locally advanced disease.

However, advancements in treatment options have significantly improved survival and quality of life for patients with both locally advanced and advanced cancer.

According to the National Breast Cancer Foundation, despite the seriousness of a Stage IV diagnosis, many people continue to live long, productive lives. Similarly, many women diagnosed with locally advanced breast cancer can expect to have good outcomes, particularly due to the array of comprehensive treatment options available.

Metastatic Vs Locally Advanced: Are They the Same?

While we’ve discussed the definitions of locally advanced and advanced cancers, it’s also important to know the distinction between locally advanced and metastatic cancers specifically.

They are related terms used in cancer staging, but they represent different stages of the disease, and recognizing the differences can enhance your understanding of the disease and its treatment.

Defining Metastatic Cancer

Metastatic cancer, often termed Stage IV cancer, is the most advanced stage of cancer.

It denotes that the cancer has spread from its original (primary) location to distant organs or tissues in the body.

For instance, if breast cancer spreads to the lungs, it would be called metastatic breast cancer, not lung cancer.

The process of cancer spreading is called metastasis. As explained by Cancer.net, metastasis happens when cancer cells break away from the primary tumor, travel through the blood or lymph system, and form new tumors in other parts of the body.

Locally Advanced Cancer: A Recap

As we have discussed, locally advanced cancer describes a stage of cancer that is larger and has spread to nearby tissues or lymph nodes but not to distant body parts.

It falls somewhere in the middle of the staging spectrum—more advanced than early-stage cancer but not as advanced as metastatic cancer.

Comparing Metastatic and Locally Advanced Cancer

So, are metastatic and locally advanced cancer the same? Simply put, no.

While both locally advanced and metastatic cancers imply that the cancer has spread, the critical difference lies in how far the cancer has traveled.

Metastatic cancer has spread far from its original location, whereas locally advanced cancer has spread only within the local region.

Why Does This Distinction Matter?

This distinction is vital as it impacts both treatment decisions and prognosis.

Metastatic cancers often require more extensive systemic treatments—like chemotherapy, hormonal therapy, or targeted therapy—because they have spread throughout the body.

In contrast, locally advanced cancers may still respond well to local therapies like surgery and radiation, in addition to systemic treatments.

The stage of cancer at diagnosis also helps provide a prognosis.

While both locally advanced and metastatic cancers present challenges, patients with metastatic cancers generally have a poorer prognosis than those with locally advanced cancers.

That said, it’s important to remember that everyone’s cancer journey is unique, and advancements in cancer treatments are continually improving the outlook for patients at all stages.

Treatments for Locally Advanced Breast Cancer

The treating strategies for locally advanced breast cancer (LABC) are designed to target the cancer cells and limit the spread of the disease.

They often involve a combination of different therapies, and the best approach may depend on several factors such as the stage and type of the cancer, the patient’s overall health, and their personal preferences.

Neoadjuvant Therapy

Neoadjuvant therapy, also known as preoperative therapy, involves administering systemic treatments before surgery.

The goal of this approach is to shrink the tumor, making it easier to remove with surgery.

It can also provide an early indication of how the cancer responds to treatment.

Neoadjuvant therapies may include chemotherapy, hormone therapy, or targeted therapies.

Surgery

Surgery is often a key component in the treatment plan for LABC.

The main types of surgery for breast cancer are:

Depending on the size of the tumor and the spread to the lymph nodes, a mastectomy may often be recommended for LABC.

Radiation Therapy

Following surgery, radiation therapy is usually administered to kill any remaining cancer cells and reduce the risk of recurrence.

This involves directing high-energy rays (or particles) at the breast and sometimes the lymph nodes.

Adjuvant Therapy

Is a treatment given after primary therapy (like surgery) to increase the chances of a cure.

It could include chemotherapy, hormone therapy, targeted therapy, or a combination thereof.

Targeted Therapy and Immunotherapy

This are newer areas of cancer treatment.

They work by specifically targeting cancer cells or stimulating the immune system to fight cancer.

These treatments can be effective against certain types of breast cancer, particularly those that overexpress the HER2 protein or are classified as triple-negative.

Hormone Therapy

Hormone therapy is another systemic treatment that can be used either before or after surgery.

This is particularly effective in hormone receptor-positive breast cancer, where it can help to reduce the risk of recurrence.

It’s crucial to remember that each patient’s treatment plan will be tailored to their specific situation.

Survival Rate for Localized Breast Cancer

The survival rate for any type of cancer, including breast cancer, can provide a general picture of what percentage of people with the same type and stage of cancer are still alive a certain amount of time after they were diagnosed.

In the context of breast cancer, the term “localized” refers to cancer that has not spread beyond the breast or the axillary (underarm) lymph nodes.

It’s worth noting that these statistics are derived from large groups of people, and they cannot predict individual outcomes.

Understanding Survival Rates

Survival rates are often expressed in term of a 5-year survival rates, which is the percentage of people who live at least this perios of time after being diagnosed with cancer.

However, many people live much longer – and many are also cured.

The 5-year relative survival rate for women with localized breast cancer is 99%.

This means that women with localized breast cancer are, on average, 99% as likely as women in the general population to live for at least 5 years after being diagnosed.

Localized vs. Locally Advanced Breast Cancer

It’s important to distinguish between localized and locally advanced breast cancer, as the terms refer to different stages of the disease:

Generally, the survival rates for locally advanced breast cancer are lower than for localized disease because LABC is more likely to have spread beyond the point of original detection, the five-year survival rate for Stage III breast cancer ranges from 72% to 85%, depending on different factors.

Hope for the Future

While the survival rates for locally advanced breast cancer are lower than those for localized breast cancer, it’s important to note that these numbers are averages and many factors can influence individual prognosis.

It’s also critical to remember that survival rates are continually improving due to advancements in detection and treatment.

Transition to CAPItello-291 Trial

While understanding the stages of breast cancer and survival rates is important, it’s equally crucial to explore how advancements in science are continually improving these survival rates.

One of the most promising areas of research in breast cancer treatment today is targeted therapy, a type of treatment that uses drugs or other substances to identify and attack specific types of cancer cells.

A prime example of this cutting-edge research is the CAPItello-291 trial, a groundbreaking clinical study focused on evaluating a combination therapy of Capivasertib plus Fulvestrant for HR+/HER2– locally advanced or metastatic breast cancer.

What is the CAPItello-291 Trial?

The CAPItello-291 trial is an international, randomized, placebo-controlled, double-blind study.

It was designed to investigate the effectiveness of a combination therapy using Capivasertib and Fulvestrant. As Hope Rugo, MD explains, “CAPItello-291 is a randomized phase 3 double-blind trial that treated patients who had hormone receptor positive metastatic breast cancer who had progressed on an aromatase inhibitor and a CDK4/6 inhibitor.“

Why is the CAPItello-291 Trial Important?

The CAPItello-291 trial represents an important step forward in the field of targeted therapy for breast cancer.

It centers around the drug Capivasertib, an AKT inhibitor.

The AKT pathway is commonly mutated in many cancers, including breast cancer, leading to increased growth and survival of cancer cells.

By inhibiting this pathway, Capivasertib has the potential to slow down or even halt the progression of the disease.

The second drug in this combination therapy, Fulvestrant, is a selective estrogen receptor degrader. It works by targeting the estrogen receptor, a common feature in many breast cancers, and degrading it, preventing the cancer cell from receiving the signals it needs to grow.

In theory, this combination could offer a powerful approach to controlling the progression of HR+/HER2– advanced breast cancer. The CAPItello-291 trial was designed to put this theory to the test.

Understanding the CAPItello-291 Trial

Now that we have established the relevance and potential importance of the CAPItello-291 trial, it is time to delve deeper into its design, patient population, and the therapeutic combination that it evaluated.

Trial Design

CAPItello-291 was an international, randomized, placebo-controlled, double-blind study.

This design is considered the ‘gold standard’ in clinical trials, as it minimizes biases and ensures the most accurate results possible.

The patients in the trial were divided into two groups:

  1. One received Capivasertib plus Fulvestrant.

  2. The other received a placebo plus Fulvestrant.

“One to one to receive Fulvestrant with either the AKT inhibitor Capivaserb or placebo“, commented Hope Rugo, MD and mentioned that the study “showed that progression-free survival was significantly improved in patients who received Capivasertib with a very nice hazard ratio for PFS.“

The use of a double-blind study design, where both the patients and the researchers do not know who received the active treatment, also helped prevent any influence of expectations on the trial’s outcomes.

Patient Population

The trial involved patients with Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative (HR+/HER2-) locally advanced or metastatic breast cancer who had seen their disease progress after treatment with an aromatase inhibitor and a CDK4/6 inhibitor.

This specific group was chosen because HR+/HER2- is the most common subtype of breast cancer, and it often becomes resistant to standard treatments over time.

As such, finding more effective treatments for this patient group is a top priority.

Investigational Therapy: Capivasertib plus Fulvestrant

The key focus of the CAPItello-291 trial was the potential of the drug combination of Capivasertib and Fulvestrant.

Capivasertib is an AKT inhibitor.

The AKT pathway is often mutated in cancers and leads to increased cancer cell growth and survival.

By inhibiting this pathway, Capivasertib can slow down or stop the progression of the disease.

On the other hand, Fulvestrant is a selective estrogen receptor degrader (SERD).

Many breast cancers are sensitive to estrogen, a hormone that can promote their growth. Fulvestrant works by degrading the estrogen receptor in these cancer cells, stopping the growth signal, and helping slow the cancer’s progression.

In summary, the CAPItello-291 trial aimed to investigate the effectiveness of this combination therapy in a specific group of breast cancer patients who had seen their disease progress despite existing treatments. The results of this trial could lead to a new standard of care for these patients and represent a significant advance in breast cancer treatment.

Study Findings

The findings from the CAPItello-291 trial offer exciting new insights into the treatment possibilities for patients with HR+/HER2- advanced breast cancer.

Primary and Secondary Endpoints

The primary endpoint of the trial was progression-free survival (PFS), a measure of how long the patients lived without their disease getting worse.

Regarding PFS, the results were statistically significant and clinically meaningful, showing a substantial improvement for patients who received Capivasertib plus Fulvestrant.

The secondary endpoints included overall survival (OS), the time until the disease progressed again after initial treatment (second PFS), and the overall response rate (ORR), which is the percentage of patients who experienced a reduction in tumor size.

These outcomes also showed a trend towards improvement with the Capivasertib and Fulvestrant combination.

According to Dr. Hope Rugo, “These findings are encouraging, as they indicate that Capivasertib, in combination with Fulvestrant, is well-tolerated and provides a potential treatment option for patients with hormone receptor positive metastatic breast cancer, particularly those who have previously received CDK4/6 inhibitors.“

Comparative Efficacy

The study also compared the efficacy of Capivasertib plus Fulvestrant versus placebo plus Fulvestrant.

The results showed a clear superiority of the combination therapy, with patients who received Capivasertib plus Fulvestrant experiencing a significantly longer time without disease progression compared to the placebo group.

This comparative efficacy data suggests that adding Capivasertib to Fulvestrant could enhance the benefits of treatment for patients with HR+/HER2- advanced breast cancer who have previously received treatment with aromatase and CDK4/6 inhibitors.

Significance of the PFS Improvement

PFS is a critical measure in cancer trials as it indicates not only survival but also quality of life.

By delaying disease progression, patients can maintain a higher quality of life for a longer period.

The significant PFS improvement observed in the CAPItello-291 trial therefore offers hope for patients looking for more effective treatment options.

Interview with Dr. Hope Rugo

Having examined the study findings, we now turn to an exclusive interview with Dr. Hope Rugo, a leading expert in the field and one of the key researchers involved in the CAPItello-291 trial.

Her insights offer a deeper understanding of the trial’s results and their potential implications for the future of breast cancer treatment.

Dr. Rugo’s Insight on the Trial Results

Discussing the significance of the CAPItello-291 trial, Dr. Rugo highlighted the potential of Capivasertib plus Fulvestrant for improving patient outcomes. “The results of the CAPItello-291 trial are eagerly awaited by the medical community, and there is hope that Capivasertib will receive regulatory approval for the treatment of metastatic hormone receptor positive breast cancer” she noted.

Dr. Rugo on the Approval of Capivasertib

Safety and tolerability are key for the approval in cancer treatment.

Discussing this aspect, Dr. Rugo explained, “The approval decision will determine whether the drug will be available for all patients or specifically for those with AKT pathway mutations. If approved, Capivasertib will offer oncologists a targeted therapy that is both efficacious and well-tolerated, addressing an unmet need in this patient population.” She further mentioned that more data would be forthcoming on the long-term safety of Capivasertib and Fulvestrant combination therapy.

Check the entire Hope Rugo’s MD interview during the ASCO 2023 here:

 

 

Conclusion

Breast cancer is a complex disease, but our collective efforts and advancements in science are continuously helping us to understand and combat it more effectively.

As we wrap up this discussion, we encourage all readers to stay informed about the latest developments in breast cancer research and treatment.

Consult with your healthcare provider for any concerns or questions related to breast cancer.

Remember, knowledge is power, and staying informed is a crucial step in maintaining good health.

Thank you for joining us in this exploration of locally advanced breast cancer and the groundbreaking CAPItello-291 trial.

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