Summary
Diagnostics have worked hand in hand with breast cancer drugs to increase survival rates of women with breast cancer. In the US, the current 5-year survival rate for breast cancer is 90%—substantially higher than the 5-year survival rate of 75% in 1975
Mammogram screening has played a key role in early breast cancer detection, whilst companion diagnostics and multiple gene prognostic assays are essential for guiding personalised treatment, which has improved outcomes for women
In 2020, 2.3 million women were diagnosed with breast cancer and 685,000 deaths resulted from the disease, according to the World Health Organisation. Diagnostics play an important role in breast cancer, as the earlier it is detected, the higher the survival rate.
Breast cancer diagnostics (or detection methods) run the gamut, from simple self-checks a woman can do at home, to more complex companion diagnostics, which are used to select targeted treatments depending on the subtype of cancer a woman has.
With diagnostics working hand in hand with treatments, breast cancer survival rates have increased over the years. In the US, the current 5-year survival rate for breast cancer is 90%—substantially higher than the 5-year survival rate of 75% in 1975.
This Breast Cancer Awareness Month (October), we summarise 6 types of breast cancer diagnostic technologies making an impact on women’s lives.
1. Screening and detection with mammography
Most Western European countries like UK or Germany sponsor mammography screening programmes for women aged around 50 to 70. However, in the US, the American College of Obstetricians and Gynaecologists (ACOG) guidelines suggest offering the choice of screening as early as 40 but to recommend starting screening no later than 50.
The goal of screening is early detection of breast cancer, which generally leads to early treatment and better outcomes.
Despite age recommendations, those with risk factors such as a family history of breast cancer may consider starting screening earlier.
According to the American Cancer Society, about 1 in 5 breast cancers are missed by mammograms. This is especially so if the woman has dense breast tissue, more common in younger women, in which case ultrasound may be preferred
2. Liquid biopsies
Liquid biopsies are less invasive compared with traditional tissue biopsies, as only a blood sample is needed, instead of surgery.
In the case of Foundation One Liquid CDx and Guardant360, a blood sample is taken, and next-generation-sequencing is then used to provide a molecular profile of circulating tumor DNA.
The Foundation One Liquid CDx has been approved as a companion diagnostic for the PIK3CA inhibitor alpelisib (Piqray) treatment in advanced breast cancer whilst a large scale study has also shown that Guardant360 effectively guides personalised therapy for metastatic breast cancer.
3. Multiple gene prognostic assays
Multiple gene prognostic assays such as the Oncotype Dx Breast Recurrence Score, MammaPrint and EndoPredict are used to assess the risk of cancer recurrence in early breast cancer patients and evaluate the potential benefit of therapies.
Such assays have been well-received by oncologists and patients in recent years as they potentially help patients avoid unsuitable treatments such as chemotherapy
EndoPredict, Oncotype DX Breast Recurrence Score and Prosigna are recommended by NICE as options for guiding adjuvant chemotherapy decisions for people with estrogen (ER)-positive, (HER2)-negative and lymph node (LN)-negative early breast cancer.
Germany reimburses Oncotype Dx (3296.50 EUR) through the national tariff list for a similar indication, whilst EndoPredict (1699.80 EUR), MammaPrint (2100,29 EUR) and ProSigna (2100,29 EUR) have been added to the reimbursement list since June 2021.
4. HER2 companion diagnostics
There are several FDA-approved companion diagnostics for breast cancer. Many are used to detect the status of the HER2 gene, as HER2 positive (HER2+) breast cancer can be treated with effective targeted treatments (e.g. trastuzumab).
Some examples of HER2 companion diagnostics for breast cancer include immunohistochemistry tests (e.g. HercepTest, InSite HER2 neu KIT), in situ hybridization tests (e.g VENTANA HER2 Dual ISH DNA Probe Cocktail etc.), fluorescence in situ hybridization tests (e.g. PathVysion HER-2 DNA Probe Kit, PATHWAY anti-Her2/neu (4B5) etc.) and chromogenic in situ hybridization tests (e.g. SPOT-LIGHT HER2 CISH Kit, HER2 CISH pharmDx Kit etc.)
In a metanalysis of studies involving 12,000 women diagnosed with HER2+ breast cancer, those who were treated with the targeted treatment trastuzumab (Herceptin) alongside other treatments were 36% less likely to have recurrent cancer and 40% less likely to die from the disease.
5. BRCA companion diagnostics
BRACAnalysis CDx is a sequencing-based companion diagnostic which detects the BRCA1,2 mutations, as such breast cancers can be treated with PARP inhibitors like olaparib (Lynparza) and talazoparib (Talzenna).
In a study of 302 women diagnosed with a BRCA mutation and HER2-negative metastatic breast cancer, olaparib lowered the risk of disease progression or death by 42% compared to chemotherapy.
With talazoparib, women diagnosed with a similar cancer subtype lived on average for 8.6 months without their disease getting worse compared with 5.6 months for patients treated with the doctor's choice of another cancer treatment.
6. PD-L1 companion diagnostics
Triple negative breast cancer (TNBC), characterised by the lack of estrogen and progesterone receptors and excess HER2 proteins, has poorer prognosis compared to other breast cancer subtypes with more established treatments.
However, promising treatments have emerged for patients who meet the PD-L1 biomarker cut-off for immunotherapy. One example of such an immunotherapy treatment is pembrolizumab (Keytruda).
In terms of diagnostics, FDA has approved the PD-L1 immunohistochemistry 22C3 pharmDx test as a companion diagnostic for selecting patients with metastatic TNBC for pembrolizumab treatment.
In a randomized controlled trial, first-line pembrolizumab in combination with chemotherapy induced a significant improvement in survival benefit over chemotherapy alone, for with those diagnosed with PD-L1 metastatic breast cancer.
As science progresses, we look forward to new biomarkers and more impactful diagnostics, which could personalise treatment and improve outcomes for patients.
This is a non-comprehensive review of breast cancer diagnostics. For more about diagnostics, drop us a mail at info@centivis.com.