Breast cancers are not all the same - they can develop, grow, and react to treatment in different ways. Shifts in molecular biology have led to the identification of various subtypes of breast cancer, each with each needing a tailored treatment approach. Luminal B breast cancer is one such subtype, requiring specialised treatment strategies.

A hormone receptor-positive cancer, Luminal B is influenced by hormones, typically testing positive for oestrogen receptors (ER) and/or progesterone receptors (PR). Recognising and understanding these differences is crucial in selecting the most effective treatment.

Molecular Subtypes of Breast Cancer

Recent technology using gene expression profiling has helped us understand the various subtypes of breast cancer. The development of this classification is based on the genes expressed in the tumour cells. These were then analysed by an algorithm for patterns of gene expression.

There are four main intrinsic molecular subtypes:

• Human epidermal growth factor receptor 2 –enriched (HER2 enriched)
• Basal-like
• Luminal A
• Luminal B

This categorisation does affect how doctors regard breast cancers in contrast to the standard way using immunohistochemistry or staining the pattern of the tumour using antibodies. There might then be some differences in the way breast tumour is grouped based on these genetic technologies or by immunostains.

HER2-Enriched Breast Cancer

HER2-enriched breast cancers, predominantly HER2-positive, may occur with or without hormone receptors. This subtype is less common, making up a smaller fraction of breast cancer cases, but is known for its rapid growth and aggressive nature, often diagnosed at more advanced stages. Despite its daunting behaviour, treatment targeting the HER2 protein has improved outcomes for some patients with this type of cancer.

The mainstays of treatment for HER2-enriched cancers include:

• Surgery
• Chemotherapy
• Radiation therapy
• Targeted therapies

Triple-Negative or Basal-Like Breast Cancer

Triple-negative or basal-like breast cancer is defined by its lack of oestrogen and progesterone receptors and absence of HER2 enhancement, making it particularly challenging to treat due to the unavailability of hormonal or HER2-directed therapies. This subtype is more frequently diagnosed among younger women and those with a BRCA1 mutation. Triple-negative breast cancer is characterised by rapid growth and aggressive behaviour.

Treatment options for this subtype are more limited and generally involve:

• Surgery
• Radiation therapy
• Chemotherapy
• Immunotherapy

Luminal A Breast Cancer

Luminal A breast cancer, often recognised for its hormone receptor-positive and HER2-negative status, is characterised by its positivity for both oestrogen and progesterone receptors while lacking HER2 expression. This subtype is noted for its low levels of the Ki-67 protein, indicative of slower cellular growth rates, which generally translates to a lower grade and a more favourable response to treatment.

Standard treatment approaches for this subtype include:

• Surgery
• Radiation therapy
• Hormonal therapy, with chemotherapy considered in certain scenarios

Luminal B Breast Cancer

Luminal B breast cancer shares the hormone receptor-positive trait but differs significantly in its potential HER2 status, being either positive or negative. This subtype is marked by higher levels of Ki-67, suggesting a quicker rate of cell division. Luminal B is also noted for its aggressive nature as these tumours often present as higher grade, larger in size, and exhibit reduced hormone receptor expression. Consequently, they pose a greater risk of recurrence and generally carry a less favourable prognosis compared to Luminal A breast cancers.

Treatment typically encompasses:

• Surgery
• Radiation therapy
• Chemotherapy
• Targeted therapy if HER2-positive

What is the Difference Between Luminal A and B?

As covered above, the hormone-positive breast cancers generally belong to the Luminal A and Luminal B subtypes. There are specific features of Luminal B compared to Luminal A breast cancers:

• Lower expression of hormone or oestrogen receptors.
• Luminal B is more likely oestrogen receptor positive, progesterone receptor negative and can be Her2 positive (ER+, PR-, HER2+).
• Higher cell proliferation or turnover based on cell markers such as Ki67. This may imply the tumour cells are more active, at least under microscopy.
• Higher histologic grade when examined under the microscope (higher histologic grade means it appears more “aggressive” or disorganised under microscopy).
• Luminal B breast cancers seem to have a worse outcome compared to Luminal A breast cancers.
• The pattern of tumour spread may involve the bone and to a lesser degree the lung for Luminal B breast cancers whereas Luminal A breast cancers tend to involve the bone primarily. Luminal B pattern of metastasis may be more similar to basal-like and HER2-enriched breast cancers.
• Luminal B hormone-positive breast cancers may have a lower percentage of hormone receptors staining on pathology. They would then benefit from both chemotherapy and hormonal therapy.

Causes of Luminal B Breast Cancer and Who is at Risk?

The specific origins of Luminal B breast cancer remain largely undetermined, yet several risk factors have been identified that may influence its development. This subtype, like other forms of breast cancer, arises from a complex interplay of genetic, lifestyle, and environmental influences.

Key risk factors include:

• Age: The likelihood of developing Luminal B breast cancer increases with age, particularly after the age of 50.
• Genetic Predisposition: A family history of breast or ovarian cancer can elevate the risk, as can the presence of inherited genetic mutations linked to breast cancer.
• Alcohol Consumption: According to Breast Cancer.org, women who consume three alcoholic beverages weekly face an increased risk of breast cancer.
• Breast Density: Women with dense breast tissue have a higher risk of breast cancer compared to those with predominantly fatty breast tissue.
• Previous Breast Conditions: Having a history of breast cancer or specific non-cancerous breast conditions can elevate the risk of developing the Luminal B subtype.
• Radiation Exposure: Previous radiation treatments to the chest area for other medical conditions can contribute to breast cancer risk.
• Reproductive History: Having children later in life, particularly after 30, or not having children at all, has been associated with a higher risk of breast cancer.
• Body Weight: Being overweight or obese is associated with a higher risk of developing many types of breast cancer, including Luminal B.
• Alcohol Consumption: Regular consumption of alcohol has been linked to an increased risk of breast cancer.

What Are the Signs and Symptoms of Luminal B Breast Cancer?

Luminal B breast cancer, like other types of breast cancer, may not always manifest with clear symptoms, particularly in its early stages. It is often detected through routine mammogram screenings before symptoms even arise.

However, when symptoms do present, they can be diverse and variable, ranging from subtle to more pronounced changes. Here’s what to watch for when it comes to breast cancer:

• Breast Lumps: Detecting a new lump in the breast or under the arm is one of the most common signs. These lumps may also appear near the collarbone.
• Texture Changes: Look out for any thickening or hardening in the breast tissue, which can feel distinctly different from surrounding areas.
• Morphological Changes: Any alteration in the size, contour, or shape of the breast should prompt further examination.
• Nipple Changes: This can include newly inverted nipples, sores, or unusual crusting and ulcers that do not heal.
• Discharge: Nipple discharge, particularly if it is clear or blood-tinged, can be a sign of deeper issues.
• Skin Alterations: Changes such as redness, puckering, dimpling, or an orange peel-like texture on the breast skin are indicative of underlying changes.
• Sensitivity: Increased tenderness or pain in the breast that differs from normal monthly changes can be a symptom.

If the cancer advances to a metastatic stage, symptoms might depend on the areas in which the cancer has spread, potentially causing additional health changes. It's essential to become familiar with the normal look and feel of your breasts, as this awareness can lead to early detection through self-exams and professional screenings. Should any changes or concerns arise, consulting with a healthcare provider or breast cancer specialist promptly can lead to an earlier diagnosis and proper treatment.

How is Luminal B Breast Cancer Diagnosed?

Diagnosing Luminal B breast cancer involves a series of assessments, much like other forms of breast cancer. The diagnostic process typically begins with imaging tests such as mammograms, which are crucial for detecting abnormalities in breast tissue. Depending on the findings from initial imaging, a biopsy might be recommended.

Key Diagnostic Tests Include:

• Imaging Tests: These may include mammograms, ultrasound, or MRI scans to visualise the structure of the breast and pinpoint areas of concern.
• Biopsy: The most conclusive test, a biopsy involves taking a tissue sample from the breast. This sample is then analysed to determine the presence and type of cancer cells.
• Receptor Testing: In the lab, the extracted tissue undergoes receptor testing to determine its hormonal receptor status (HR status). This identifies whether the cancer cells possess receptors for oestrogen or progesterone.
• HER2 Status: Another crucial test, HER2 testing categorises the cancer based on its HER2 protein levels, which can influence treatment options. HER2-negative results are shown with scores of 0 or 1+, while a score of 3+ indicates HER2-positivity. An equivocal score of 2+ may require further testing to clarify HER2 status.
• Ki-67 Protein Levels: This marker helps gauge how quickly the cancer cells are growing by measuring the proliferation rate of the cells. Higher Ki-67 levels suggest a more aggressive cancer.

How is Luminal B Breast Cancer Treated?

There has been much publicity about using targeted therapy for cancer treatment. What is the first “targeted” therapy for breast cancer?

Well, actually, it should be endocrine or hormonal therapy. The development of treatments using medication that targets the oestrogen receptor expressing breast cancers is one of the shifts for oncology. More than a century ago, it was found that ablating or removing the hormonal function of the ovaries, pituitary or adrenals was a way to treat some advanced breast cancer patients. It was not until about 50 years ago that there were steroid hormone receptors, known as oestrogen receptors (ER) and progesterone receptors (PR), that the tumour expressed that mediated this benefit.

The ER expressing or ER positive breast cancer is then the target for anti-oestrogen therapies. Drugs were subsequently developed to act on the oestrogen receptor pathway. Some of these drugs include SERMs (Selective Estrogen Receptor Modulators), and aromatase inhibitors.

Table 1: Drugs that target the hormonal pathway in breast cancer

• Tamoxifen (Nolvadex)
• Toremifene
• Anastrozole (Arimidex)*
• Letrozole (Femara)*
• Exemestane (Aromasin)*
• Fulvestrant (Faslodex)
• Leuprolide (Lucrin) or Goserelin (Zoladex)
• Megestrol acetate (Megace)

*These are aromatase inhibitors

Currently, for ER-positive breast cancer or hormone-responsive breast cancer, the use of anti-oestrogen treatment with these drugs is important and has saved many lives worldwide. Women with early stage endocrine receptor positive breast cancer would now take at least 5 years of adjuvant hormonal therapy to reduce recurrence and improve survival.

Recent data even suggests that longer durations of adjuvant endocrine therapy (such as the ATLAS trial using tamoxifen for 10 versus 5 years) will benefit women as some of these ER positive cancers do relapse later than the typical 5 years that are mentioned and tracked in studies.

What is the Survival Rate for Luminal B Breast Cancer?

The survival rate for Luminal B breast cancer can vary widely, influenced by numerous individual factors. Key elements that shape the prognosis include a patient's age, overall health condition, the grade and stage of the tumour at diagnosis, HER2 status, any inherited genetic variations, menopausal status, previous cancer treatments, and the patient’s response to these treatments. As such, each case is unique, and survival rates can differ significantly based on how these factors interact.

Navigating Breast Cancer and Getting the Right Help

In summary, breast cancer classification and treatment are undergoing many changes. What we understand as hormone responsive or oestrogen receptor positive breast cancer has been shown by next generation sequencing (NGS) and other technologies to comprise at least 2 subtypes of breast cancer. Luminal A and Luminal B breast cancers have distinct features, and the growth of such tumours is driven by different oncogenic mechanisms.

Gaining an understanding of these variations is crucial in developing tailored treatment strategies that can significantly enhance patient outcomes.

“Expert knowledge means better care for cancer”

Written by:

Dr Peter Ang
MBBS (Singapore)
MMed (Int Med)
MRCP (UK)
FAMS (Medical Oncology)