Reassuring our breast cancer survivors - what’s the real risk of a second primary?

Sarah, a 58-year-old woman, came to see you last year with a new breast lump. She had no family history of breast or ovarian cancer. You examined her promptly, referred her urgently and she was diagnosed with breast cancer.  Fortunately, it was caught early and she had local, stage 1 disease treated successfully with lumpectomy and radiotherapy. She recovered well and was reassured by her oncology team that the risk of recurrence or metastases was low.

Now, a few months later, she’s back in your consulting room. She’s well, very grateful to you for the prompt diagnosis and referral, but she is anxious about the future. She asks:

• “What’s my risk of getting another new cancer?”
• “Should I consider a double mastectomy to be safe?”
• “Has the radiotherapy increased my risk of lung cancer?”

These are not uncommon questions that our patients reasonably put to us. Over the years I’ve noticed that while we, as clinicians, often focus on the risk of recurrence or metastatic spread, our patients often fear the possibility of another new cancer arising from nowhere: that horrible fear that “lightning could strike twice.”

Until recently we’ve had little robust data to help us answer Sarah’s concerns clearly, but a recent landmark new paper McGale et al., BMJ 2025;390:e083975 has now provided the most comprehensive data yet on second primary cancers after breast cancer, discussed further in a linked editorial. This population-based study followed 475,000 women in England with early invasive breast cancer treated with surgery between 1993 and 2016, with follow-up to 2021. It’s a massive, methodologically rigorous piece of research and, importantly, its results are reassuring for both patients and clinicians.

The key findings were:

• Non-breast cancers: By 20 years, 14% of women had developed a new non-breast cancer (most commonly uterine and lung), compared with 12% expected in the general population an absolute excess risk of just 2%.
• Contralateral breast cancer: 6% developed a new cancer in the opposite breast, compared with 3% expected an absolute excess of only 3%. The excess was slightly higher in younger women, and in those with larger or node-positive tumours.
• Adjuvant therapies: Radiotherapy was linked to a small increase in contralateral breast and lung cancers; endocrine therapy slightly increased uterine cancer risk but reduced contralateral breast cancer; chemotherapy increased the risk of acute leukaemia. Overall, adjuvant treatments accounted for only around 2% of all second cancers and trials show that the benefits far outweigh these small risks.
• Caveats: The study did not include family history, genetic predisposition, or lifestyle factors such as smoking or obesity all of which are obviously important for personalised risk discussions.

So, we can reassure Sarah that her long-term outlook is excellent.

• Her chance of a second primary cancer is only slightly higher than that of women who have never had breast cancer.
• The risk from radiotherapy is minimal, and should be even smaller with modern, targeted techniques.
• The highest risk is of another breast cancer, but the absolute excess is only about 3% over 20 years. It will always be a personal decision, but for most women this will not be enough to justify preventive mastectomy in the absence of strong genetic risk factors, but it does of course justify continued long-term surveillance including regular mammography.

Our role is to maintain ongoing follow-up, encourage healthy lifestyle changes to mitigate cancer risks (e.g. smoking cessation, regular exercise, weight control, moderate alcohol), to provide balanced reassurance along with an open mind and prompt assessment of any possible new cancer symptoms. 

Sarah had assumed that her risks were much higher than this, so she leaves your consulting room much happier than when she came in which is very satisfying for both of you!