Triple-Negative Breast Cancer (TNBC): Symptoms, BRCA Risk, Diagnosis and Latest Treatment Advances Understanding Triple-Negative Breast Cancer (TNBC) Triple-negative breast cancer (TNBC) is biologically and clinically different from other forms of breast cancer because it lacks three key biomarkers on the surface of the cancer cells: oestrogen receptors, progesterone receptors, and the HER2 protein, explains Dr Tan, breast surgeon. These biomarkers are important because they allow doctors to classify breast cancer into three broad categories: hormone receptor-positive cancers, HER2-positive cancers, and triple-negative cancers.Each category behaves differently and requires different treatment approaches. Hormone receptor- positive cancers, for example, may respond to hormone-blocking therapies, while HER2-positivecancers can be treated with HER2-targeted drugs. TNBC, however, doesn’t carry these treatment targets, making its management clinically different from many other breast cancer subtypes. Because of this, testing for these biomarkers forms a critical part of breast cancer diagnosis, helping doctors determine the most appropriate treatment strategy for each patient. Why TNBC Can Be More Agressive TNBC is often described as more aggressive because, among the three major categories of breast cancer, it tends to grow more quickly and spread earlier when left untreated. At the same time, TNBC is also considered relatively chemosensitive, meaning many tumours respond fairly well to chemotherapy. This creates a complex clinical picture where some patients may experience a strong initial response to treatment, while others later develop more challenging disease patterns. Although many TNBC tumours can be treated successfully, some unfortunately have a tendency to recur aggressively in other parts of the body, creating greater treatment challenges than other breast cancer subtypes. This can occur even when the tumour initially responds well to treatment. While chemotherapy may eliminate most cancer cells, it may not eradicate every single one. Some surviving cancer cells can gradually develop new mutations that make them more resistant to treatment over time. Eventually, these resistant cells may begin multiplying again and manifest as recurrent disease. This phenomenon isn’t unique to TNBC and can occur across many cancer types. However, TNBC relapses tend to occur earlier, often within the first few years after treatment, compared with hormone receptor-positive breast cancers, where recurrence can sometimes happen many years or even decades later.Signs and Symptoms to Watch For One of the most common early signs of TNBC is a self-detected lump in the breast or underarm, says Dr Tan. The underarm lump may represent an enlarged lymph node. Unlike what many people assume, cancerous breast lumps are often painless, and in TNBC, the lump may increase in size relatively quickly. The absence of pain can sometimes create a false sense of reassurance, causing some women to delay seeking medical attention.TNBC can also be more difficult to detect on routine screening mammograms because it often doesn’t produce the abnormal calcifications commonly seen in other breast cancer subtypes. This means TNBC may occasionally be missed during its earlier stages, particularly in women with dense breast tissue. As a result, a recent normal mammogram shouldn’t discourage women from seeking medical evaluation if they notice a new breast lump or unusual change. When symptoms persist despite a normal mammogram or initial reassurance, further evaluation may still be necessary. A physical examination, along with additional tests such as an ultrasound or breast MRI may be recommended, particularly for younger women with dense breast tissue. If the clinical or imaging findings raise concern for possible malignancy, a breast biopsy may then be required to confirm the diagnosis. Another less common but important presentation is inflammatory breast cancer, which can cause sudden breast swelling, redness, warmth, or mild tenderness that may initially be mistaken for an infection or inflammation. While empirical antibiotics may sometimes be prescribed first, persistent symptoms that don’t improve should be evaluated further by a breast specialist. Dr Tan adds that TNBC also tends to occur more frequently in younger women, including those below the age of 40, which is younger than the typical age at which routine breast cancer screening begins. This makes breast awareness especially important, even among younger women who may not consider themselves at risk. The Role of BRCA and Genetic Testing TNBC is sometimes associated with inherited genetic mutations, particularly BRCA1 and BRCA2, which are among the most common genetic mutations linked to hereditary breast and ovarian cancers. TNBC is especially associated with BRCA1 mutations, particularly when breast cancer develops at a younger age, such as before the age of 50. The presence of a BRCA mutation can influence both surgical decisions and systemic treatment strategies. It may also have important implications for the long-term cancer risk of other family members, making genetic counselling and testing an important consideration in selected patients. Genetic testing is often recommended for women diagnosed with breast cancer under the age of 50, including those with TNBC. It may also be considered in women who develop cancer in both breasts, have a personal history of more than one cancer, or have a strong family history of breast, ovarian, or certain other cancers. A positive BRCA result means that even after successful treatment of the initial breast cancer, there remains an increased risk of developing a new primary cancer in the future due to the underlying inherited genetic predisposition. It can also influence several aspects of long-term management, including: • The use of certain targeted cancer drugs designed for BRCA-associated breast cancers• Surgical planning, where some patients may consider bilateral mastectomy rather than breast- conserving surgery• Long-term surveillance of other high-risk organs, particularly the ovaries • Discussions around preventive surgery, including removal of the ovaries and fallopian tubes in selected patients The implications can also extend to family members, as relatives may potentially carry the same BRCA mutation. When a patient is found to have a BRCA mutation, family members may also be advised to undergo genetic testing. Those who are subsequently found to carry the mutation may include:• Earlier and more intensive cancer surveillance, including breast screening from a younger age using mammograms, ultrasound, and/or breast MRI • Ovarian cancer screening using blood tests and ultrasound • Consideration of preventive surgeries such as risk-reducing double mastectomy or removal of the ovaries and fallopian tubes in appropriate clinical settings Advances in TNBC Treatment One of the major advances in TNBC treatment has been a shift towards using neoadjuvant chemotherapy, where chemotherapy is given before surgery rather than after, notes Dr Tan. This approach allows doctors to assess how well the tumour responds to treatment, which can then help guide and tailor subsequent treatment decisions after surgery.Using chemotherapy upfront may also help shrink the tumour, improving the chances of breast- conserving surgery rather than requiring more extensive surgery. In patients whose TNBC hasspread to the underarm lymph nodes, neoadjuvant chemotherapy can sometimes downstage the cancer sufficiently so that fewer lymph nodes need to be removed during surgery. This represents an important change from previous practice, where routine removal of all underarm lymph nodes was more common and carried a higher long-term risk of complications such as lymphoedema, a chronic swelling condition that can affect the arm. Another important advancement is immunotherapy, which works by targeting immune-related proteins that cancer cells use to evade the body’s immune system. Dr Tan adds that immunotherapy, when combined with neoadjuvant chemotherapy, has been shown to significantly improve survival outcomes in selected patients with TNBC. Patients with higher-risk TNBC are more likely to be considered for immunotherapy. Factors such as tumour size, lymph node involvement, and other markers suggesting a higher risk of recurrence are often taken into account when determining suitability for these newer treatments. With the addition of immunotherapy, studies have shown improved response rates and better overall survival outcomes in selected patients with TNBC. Several newer drug classes have also shown promising results in clinical trials and are expected to become part of mainstream TNBC treatment over time. Despite the aggressive nature of TNBC, there has been a significant leap in medical treatment over the past decade, leading to improving clinical outcomes for many patients.Expert ContributorDr Tan Yah Yuen Senior Consultant & Breast Surgeon Solis Breast Care & Surgery Centre, Singapore http://www.solis.sg/ http://www.instagram.com/solisbreastcare Article reviewed by Dr Tan Yah YuenOriginally published on Expert-led Health, Fitness & Nutrition Insights. Republished with permission.