Roche breast cancer solutions

The term “breast cancer” refers to a malignant tumour that has developed from cells in the breast. Breast cancer occurs when cells in the breast grow abnormally—dividing and multiplying unmanageably. While breast cancer occurs in both men and women, it occurs disproportionately in women—specifically, 100 times greater in women than men, and is the most common type of cancer in women.¹ Breast cancer ranks second in cancer deaths among women, with an estimated 2.26 million new cases in 2020.² It is estimated in developed nations that a woman's lifetime risk of breast cancer can be as high as 1:7.³

Most risk for breast cancer is due to ageing or environmental exposures. However, some women may have inherited genetic mutations such as a BRCA gene that greatly increase the risk.⁴

Breast cancer prevention

85-90% of breast cancers are due to genetic abnormalities that happen as a result of the body’s aging process or varying conditions that increase risk.⁵ Mammography, clinical breast exam, and magnetic resonance (MRI) or ultrasound imaging are screening methods that aid in finding disease early. Clinical guidelines about frequency and recommended age to start screening will vary country to country.

5-10% of cancers are due to an inherited abnormality that puts women at increased risk.⁷ For patients with a family history of breast or ovarian cancer or from Ashkenazi Jewish ancestory, testing for genetic mutations in the BRCA1 or BRCA2 genes may help determine if they are at increased risk, in which case certain preventive measures may be taken, to stop cancer before it develops.

Breast cancer diagnosis 

There are different locations of where a breast tumour is found. A tumour may start to develop in the lobules, which are the milk-producing glands, or it can begin in the ducts, the passages that drain milk from the lobules to the nipple. Sometimes breast cancer will begin in the stromal tissues, which include the fatty and fibrous connective tissues of the breast. 

The diagnosis of breast cancer usually happens after a mass is detected during screening, after a biopsy sample is obtained. A pathologist will confirm whether a tomour is benign (harmless) or malignant (cancerous) based on laboratory analysis. Samples of tissue containing breast cancer cells are removed during a biopsy or surgery. There are four types of biopsy that may take place:

• Excisional biopsy: The removal of an entire lump of tissue.
• Incisional biopsy: The removal of part of a lump or a sample of tissue.
• Core biopsy: The removal of tissue using a wide needle.
• Fine-needle aspiration (FNA) biopsy: The removal of tissue or fluid, using a thin needle.

A patient’s overall prognosis and treatment decisions will be based on diagnostic testing, and other factors such as:

• The stage assessment of the cancer (based on the size of the tumor and whether it is in the breast only or how far it may have spread to lymph nodes or other places in the body) and histologic type and subtype (hormone receptor profile)
• Where the tumour is located
• How fast the tumour appears to be growing
• A woman’s age, general health, and menopausal status
• Whether the cancer has just been diagnosed or is recurring

Roche’s advanced immunohistochemistry (IHC), in situ hybridization (ISH) and real-time polymerase chain reaction (PCR) diagnostic solutions empower personalized healthcare in breast cancer. Additionally, next generation sequencing (NGS) can unlock information about a tumour’s genetic profile. Innovations in molecular and sequencing technologies enable testing to be done not only from biopsy tissue samples, but also from more minute traces of tumour DNA that might be circulating in the bloodstream of a patient (ctDNA).

A biopsy can provide crucial information that aids diagnosis, prognosis, and prediction of response to treatment.

From the biopsy sample, a pathologist can determine whether the cells have specific receptors, which are biologically active molecules found on the surface of the cell. The presence or absence of these receptors serve as biomarkers that can be used to help predict how well a patient will respond to certain therapy options.

• Estrogen receptor (ER). If the breast cancer cells have estrogen receptors, the cancer cells are called ER positive (ER+). If the breast cancer cells do not have estrogen receptors, the cancer cells are called ER negative (ER-).

• Progesterone receptor (PR). If the breast cancer cells have progesterone receptors, the cancer cells are called PR positive (PR+). If the breast cancer cells do not have progesterone receptors, the cancer cells are called PR negative (PR-).

If there are more estrogen and progesterone receptors than normal, the cancer is called estrogen and/or progesterone receptor positive. The test results show whether treatment to block estrogen and progesterone may stop the cancer from growing.

• Human epidermal growth factor type 2 receptor (HER2/neu or HER2). If the breast cancer cells have larger than normal amounts of HER2 receptors on their surface, the cancer cells are called HER2 positive (HER2+). If the breast cancer cells have a normal amount of HER2 on their surface, the cancer cells are called HER2 negative (HER2-). HER2+ breast cancer is more likely to grow and divide faster than HER2- breast cancer.

HR stands for hormone receptor and means that tumor cells have receptors for the hormones estrogen or progesterone, which can promote the growth of HR+ tumors. HER2 stands for human epidermal growth factor receptor 2. HER2+ means that tumor cells make high levels of a protein called HER2/neu, which has been shown to be associated with certain aggressive types of breast cancer. HER2 immunohistochemistry results are given a quantification score. Those with 2+ assessments may be further assessed using an In-Situ Hybridization assay (IHS) to localize a sequence of DNA or RNA in the biological sample. IHS gene amplification results help determine HER2 gene status ad assist pathologists in identifying patients eligible for treatment with certain HER2 targeted therapies.

The four main female breast cancer subtypes, can be categorized as follows, in order of prevalence:

• HR+/HER2- (70% of cases)^4,5
• HR-/HER2-
• HR+/HER2+
• HR-/HER2+

If the breast cancer cells do not have estrogen receptors, progesterone receptors, or a larger than normal amount of HER2 receptors, the cancer cells are called triple negative. In addition to HER2, ER and PR, there are a variety of additional IHC breast markers that are used by pathologists to help differentiate between cancer subtypes, assess proliferation and identify metastasis.

A HER2-low IHC test provides a scoring algorithm to help pathologists identify "low expressors" of HER2 who may now be determined eligible for a HER2-targeted treatment option that demonstrated potential to significantly improve outcomes.⁶

In addition to an immunohistochemical biomarker profile of a breast cancer tumour determined by a pathologist using formalin-fixed paraffin-embedded (FFPE) samples, there are also clinically proven and validated molecular tests targeting a tumour’s DNA. These types of diagnostic tests look for genetic mutations to further help aid therapy decisions.

These developments, also termed “liquid biopsy” are welcome because it can be difficult to obtain enough tissue from the biopsy for multiple tests; and in some cases, it may not be possible for patients to undergo standard tissue biopsy procedures due to their health or the location of the tumour.

One example is with PIK3CA mutations that are found in close to 40 percent of estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancers.^8-10 The current standard treatment for patients with HR-positive, HER2-negative advanced breast cancer is endocrine therapy, with or without the use of a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor.^11-13 However, most patients will develop acquired resistance to endocrine-based therapy.^14,15 For these particular patients, if a tumor is found to have a PIK3CA mutation, additional treatment options that specifically target the mutation in the PIK3CA gene, are opened up.

Approximately half of all patients with metastatic breast cancer express lower levels of HER2, which historically classified them as HER2-negative, leaving them with no targeted treatment options and little hope. Algorithm developments now allow for determination a of "HER2-low" expression score for patients with metastatic breast cancer. In October 2022, the U.S. FDA approved the PATHWAY anti-HER2 (4B5) immunohistochemistry (IHC) test to help pathologists identify “low expressors” of HER2. For patients assigned a HER2-low status using a lower cutoff threshold, they become eligible for HER2-targeted treatment options, which have the potential to significantly improve outcomes.¹⁶