Author:

Nicolò Morina

Abstract

Breast cancer is one of the malignancies we know the most about, and its treatment has shown a significant progression over the years, in terms of surgical strategies, adjuvant therapies and prevention. Nonetheless, when it comes to breast cancer in older patients, it’s a different story: there is still a worrying gap in knowledge, that can often translate into a disparity in treatment, not ensuring the best therapeutic options. This gap can also foster false beliefs and personal opinions in the clinical environment, since older patients might be considered too frail to receive a specific treatment just because of their age. For these reasons, there has been a growing focus on this topic in recent decades, with inspired physicians and institutions making a great effort to develop comprehensive screening tools, inclusive clinical trials and dedicated studies, to provide objective assessments, proper treatments and, most of all, respect for older patients and all their needs.

Breast cancer sadly ranks among the most common tumours, both globally and among women. According to the estimates for 2022 provided by GLOBOCAN, the statistical tool used by the International Agency for Research on Cancer (IARC) and shown through the Global Cancer Observatory, breast cancer is the second most diagnosed cancer, accounting for 11,6% of all cancer diagnoses worldwide, just behind lung cancer (12,4%). But if we limit the data to just female tumours, breast cancer takes the top spot, in terms of both incidence and mortality, while lung and colorectal cancer take second and third place, respectively (Bray et al., 2024).

As the global population progressively ages, and since age itself is a risk factor for the insurgence of tumours, it follows that the percentage of cancer cases among older people is set to rise as the years go by. For breast cancer, more than 30% of all diagnosed patients is over 70 years old at the present day. Among the most frequent subtypes of breast cancer, about 80% of patients who are 75 years old or more might develop a luminal breast cancer, hormone receptor (HR)-positive and human epithelial growth factor receptor 2 (HER-2)-negative, more than in the younger population (about 65% in patients <50 years). This tumour subtype, if compared to HER2+ breast cancer (HR+ or -/HER2+), triple negative (HR/HER2, oestrogen and progesterone receptor-negative) and HR-/HER2+ breast cancers, usually shows more favourable biological features and advantageous treatment options (Lemij et al., 2023).

Comprehensively, these considerations should shine a spotlight on how breast cancer is treated in older people, with consequent literature and data providing consistency to treatments and support to clinical decisions for each patient. Unfortunately, this is not the case in many clinical contexts, due to a plethora of different reasons that put together have created a great obstacle to the amelioration of treatments for older patients over the decades, from surgical options to the optimal choice of adjuvant therapies. These reasons will be covered in the present article but can be generally summarized as follows: older patients are often not receiving the most appropriate treatments precisely because of their age and perceived frailty. Nevertheless, a parallel effort to overcome and change a paradigm based more on prejudice and false beliefs than on verified data has been pursued by a number of clinicians, driven by the desire to gain a thorough understanding of the characteristics of breast cancer in older patients, and to restore dignity to individuals who are all too often overlooked simply because of their age.

The delicate matter of surgery and the need for screening tools for frailty

When discussing treatment of solid tumours, either in young or older patients, the first approach to be considered is usually surgery, aiming to the removal of neoplastic cells from the site of interest. Many people are unaware of the extent to which surgery remains fundamental to modern cancer care. In a recent study, considering over 1 million tumour patients from England between 2009 and 2013, with a subsequent observation time of 5 years, it was calculated that surgery was performed in 80% of the subjects who survived until the end of the follow-up period, 38% of whom received only this treatment, without the further need for radiotherapy or chemotherapy (Mee et al., 2023). Generally, the decision of treating a tumour through either surgery or other approaches, or even a combination of them, should be based on a thorough and comprehensive evaluation of patients, considering their fitness, age, the presence of comorbidities, and their opinion, too. But when discussing cancer treatment in older patients, it is necessary to consider a higher complexity, which is not limited simply to clinical observations based on verified data, but also involves a degree of subjectivity that can have a decisive influence on the assessment of each individual case. This subjectivity regards the way an old individual can be perceived and often associated to a concept of innate frailty due to his or her age, potentially becoming an important bias when the clinician opts for a therapeutic strategy.

This issue concerns the entire field of geriatric oncology and has been the subject of discussion over the years, including in the specific context of breast cancer and surgical approach. One the leading actors of this story is Prof. Dr. Riccardo Audisio, whose long career as surgeon in Italy, UK and Sweden has enabled him to see and foster a change in this clinical environment. “The first experience I had dates back to 1992, witnessing the hasty decision not to remove a colon tumour from a patient just because she was too old, even if she was fit enough to go swimming”, remembers Audisio. That woman died a few years later from the complications of this tumour: “I thought about how much pain could have been spared if a better evaluation had been carried out”, he says. This example reflects a widespread attitude towards older patients with a diagnosis of tumour, as Audisio confirms: “It’s a general rule of thumb which is still present nowadays, a rough emotional assessment that clinicians could be tempted to follow, sometimes performing CAT exams without even talking to the patient”. Given that he had experienced this situation first-hand since the start of his career, Prof. Audisio devoted part of his efforts to the development of specific screening tools for the assessment of frailty, to help clinicians taking the best decision possible for older cancer patients.

During the 1990s, the potential discrimination faced by older patients became object of studies, analysing the issue in clinical contexts. It was recognized that treatment decisions might be based on personal opinions and assumptions, instead of objective evaluations of risks and benefits. Furthermore, it was acknowledged that older patients were often not included in clinical trials, thus negatively influencing the development of ad hoc therapies (including surgery), which might be denied just because of the age of the patient. And this despite promising results were emerging: for example, in a study on the treatment of gastrointestinal tumours in patients 65 years old or more, it was shown there were similar outcomes in complication rates and hospital stay compared to younger patients after surgery, while the differences in survival after five years were not significant when deaths unrelated to cancer were excluded (Audisio et al., 1997).

A way to measure the influence of a disease on a patient’s daily life is the performance status (PS) scale, developed by ECOG (Eastern Cooperative Study Group) and still in use today (Oken et al., 1982). This tool is useful, since it allows to track the general conditions of an individual and to distinguish among different patients when planning clinical trials. Nevertheless, it does not take into account several factors that can have a crucial impact on patients’ life, especially older ones. The need to properly assess the conditions of older cancer patients, thus considering not only age, but the whole status of the individual, prompted an Italian group to develop a new screening tool, the CGA (Comprehensive Geriatric Assessment) (Monfardini et al., 1996; Repetto et al., 2002). This tool is defined as a multidimensional, multidisciplinary process that identifies a person’s medical, social and functional needs, followed by the development of an integrated and coordinated care plan to address these needs (Parker et al., 2018). It’s an assessment that directly involves the patient and helps the clinician getting a full picture of the situation, with more information than the PS scale alone, thus allowing a better distinction between frail and fit patient (Repetto et al., 2002). Nonetheless, the CGA takes some time to be carried out, which make it not feasible or necessary for every patient. Thus, the following step was the design of a new and faster procedure, in which once again Prof. Audisio was involved together with the International Society of Geriatric Oncology (SIOG). Their efforts led to the development of PACE (Preoperative Assessment of Cancer in the Elderly), a 20-minute interview incorporating elements from the CGA, the PS and an anaesthesiologist’s evaluation of operative risk. PACE proved to be a tool as simple as effective for making an appropriate assessment of an older cancer patient’s suitability for surgery and subsequent treatments (Audisio et al., 2008). Over the years, other assessment procedures were developed in Europe, like the G8 and the fTRST (Flemish Triage Risk Screening Tool) to predict functional decline and overall survival (Kenis et al., 2014), providing clinicians with short and easy to administer tools. “These screenings should progressively become a part of clinical routine in older cancer patient’s assessment,” says Audisio, “also to avoid the risk of overtreating a frail individual or, vice versa, to undertreat a fit one just because he or she is considered too old”.

Surgery in older breast cancer patients

All the above-mentioned screening tools for frailty are useful also for the evaluation of older breast cancer patients, but compared to other solid tumours, decisions regarding surgery do not mainly focus on the potential lethality of the intervention. Instead, they consider more the consequent quality of life of the patient. Prof. Audisio explains this: “Surgery on breast cancer is less dangerous than on other tumours, since it is a subcutaneous malignancy, not visceral. Nonetheless,” he continues, “breast cancer has unique traits that must be considered: the cosmetic outcome of treatments and the social and psychological impact. These aspects have their weight in the quality of life, thus requiring that the complete removal of cancer cells through surgery must be carried out as effectively as possible, without being overly invasive, and preserving the cosmetic outcomes whenever possible”. Another crucial factor is the potential hormone sensitivity of breast tumours, which is more common in older patients and make them treatable through endocrine therapy (Lemij et al., 2023). “It’s excellent to have a wider range of therapeutical options,” says Audisio, “however, surgery should not be ruled out from the outset, as it can more effectively prevent painful relapses than other treatments”. In this regard, a UK-based study confirmed the advantages of surgery followed by adjuvant therapies in women 70 years old and more, both in terms of therapeutic outcomes and cost-effectiveness, apart from very frail patients over the age of 90 (Holmes et al., 2021): a further reminder of the importance of properly assessing patients.

Nowadays, the preferred surgical option for early breast cancer is lumpectomy rather than total breast removal (known as mastectomy): the breast-conserving approach is recommended when it is possible to achieve clear resection of margins (Fricker, 2022). Despite the safety and steady improvements that have characterised breast surgery over the years, it has nevertheless been observed that older patients tend to undergo fewer conserving procedures than younger ones. In countries like UK, policy requires that the only justifications for different cancer treatments by age must be related to patient choice or poor health conditions. In this regard, a prospective cohort study was carried out in 2014, showing that in patients 85 years old or more, the lower rates of surgery persisted even though the patients had given their consent and were fit enough to undergo surgical treatment (Lavelle et al., 2014).

These results would confirm that an age-related bias is still present in the decision-making process and could also motivate the general high variability in rates of surgery and adjuvant therapies between breast units. This is one of the issues that some pivotal research tried to analyse in a comprehensive way: an example is the “Bridging The Age Gap”, a multicentre cohort study based in UK, that from 2013 to 2018 recruited 3416 women 70 years old or more with high-risk early breast cancer. Indeed, it aimed to identify factors influencing treatment selection for these patients, as well as to assess the outcomes from surgery and other therapies. Among the key findings, it was observed that surgery remains the preferred choice by clinicians, but it must be supported by tools for the frailty assessment of the patient, since the impact on quality of life and independence in the long-term can be significantly affected (Collins et al., 2017; Morgan et al., 2020; Wyld et al., 2021). Furthermore, there might still be a negative selection bias in the performance of complex oncoplastic surgery, like post mastectomy breast reconstruction or therapeutic mammoplasty options, since women over 70 generally receive less of these treatments than younger patients, despite the results in tolerance and quality of life are similar (Quddus et al., 2023).

The evolving landscape of adjuvant treatments for early breast cancer in older patients

A full picture of the best approach to geriatric breast cancer requires a major understanding of the outcomes that different treatments and their combination can produce. The last years were characterised by a growing awareness of the lack of knowledge in this field, which big studies like the “Bridging The Age Gap” one have sought to address. This is also recognised in the case of adjuvant therapies. Prof. Dr. Etienne Brain, medical oncologist with a strong background in adjuvant and neoadjuvant treatments for breast cancer, has experienced these shortcomings since the end of the 1990s, and is still working to bring about a change in clinical knowledge and mindset. “At the beginning of my career, there was a deep lack of literature on the management of breast cancer in older people,” he says, “and that resulted in a lack of guidelines as well”. He continues: “My first realisation was that it was extremely difficult to choose the right therapy in terms of drugs, considering the different levels of tolerance to treatment intensity that each patient can show”. At the bases of this issue there is a great contradiction, as already pointed out: most people with breast cancer are over 65 or 70 years old, while most of the clinical results rely on trials carried out on younger patients. As Brain confirms, “the big challenge was to convince people that things had to change, and rules of practice, frequently deriving from prejudice-based evidence, should not be applied anymore”.

Over the years, Prof. Brain has witnessed and contributed to a progressive change occurred in France, through institutions like the French Breast Cancer Intergroup Unicancer (UCBG) and Institut Curie, as well as in Europe: “The presence of influential people like Matti Aapro, Silvio Monfardini, and Riccardo Audisio, made easier to share an international awareness and create a network on the topic, also through the SIOG”, he states. In this regard, the European contribution also reached the US, thanks to the important involvement of figures like Dr. Martine Extermann and Dr. Lodovico Balducci in the American Society of Clinical Oncology (ASCO).

Overall, the efforts made have started to shed a light also on the effects, risks and benefits of adjuvant treatments, a matter of crucial importance for such a variable tumour as breast cancer. Among the achievements of which Prof. Brain is most proud, the recent results from the ASTER70 trial surely stand out. Between 2012 and 2016, this phase III study performed a genomic screening on 1969 patients aged 70 years or older, to identify those with high-risk oestrogen receptor-positive HER2-negative breast cancer: 1089 women with these characteristics were randomised to receive either a combination of hormonotherapy and chemotherapy, or just the hormonotherapy. The trial was aimed at assessing the role of chemotherapy in the treatment of these tumours, since its effects have long been the subject of debate. In fact, it showed that adding chemotherapy does not improve patients’ overall survival; on the contrary, it can increase toxicity and adverse events (Brain et al., 2025). “This trial sends a big message,” says Brain, “since it’s clear that chemotherapy can’t be the priority, at least for luminal breast cancer, for which the endocrine therapy remains the best option as adjuvant treatment”. He continues: “If chemotherapy has a potential benefit for this type of tumour, it is certainly marginal, and we still don’t have the tools to determine which patients would take advantage from it”. The potential de-escalation of chemotherapy could represent a major shift in the field: “It remains to be seen whether this will be welcomed everywhere,” wonders Brain, “but we have to remember that adjuvant treatments are aimed at prevention, so overtreatment should always be avoided”. Returning to ASTER70, it is also worth emphasising the robustness of the trial’s selection phase: no subjective decisions, no bias, only the patient’s genomic profile and a further stratified randomisation using the G8 tool for geriatric assessment.

The rationale, design and results of the ASTER70 study provide a clear example of the way forward to ensure sound clinical decision-making regarding breast cancer treatment in older patients. Indeed, it had already be pointed out that anticancer drugs might not be as well tolerated by older people as previously thought, since our knowledge on the subject stemmed from studies conducted predominantly on younger patients, or, at most, in fit older ones, with a potential high variability in terms of physiology compared to frail individuals or those with comorbidities (Wildiers & de Glas, 2020). Other notable studies are comparing chemotherapy regimens with new chemotherapy-free solutions, showing their primary results in the last years. The randomised phase II TOUCH trial from the IBCSG (International Breast Cancer Study Group) investigated the effects of palbociclib for the selective inhibition of CDK4/6 enzymes, letrozole to reduce oestrogen production through the inhibition of aromatase enzyme, and the subsequent combination of the monoclonal antibodies trastuzumab and pertuzumab for the dual blockade of HER2, in postmenopausal patients with luminal B breast cancer (HR+/HER2+). This treatment appears to be a promising alternative to the standard chemotherapy approach based on paclitaxel followed by the monoclonal antibodies for HER2, since similar pathological responses were achieved, with the need to evaluate the outcomes in the long-term (Malorni et al., 2026). The ongoing “Appalaches” study, promoted by the EORTC (European Organization for Research and Treatment of Cancer) is also assessing the adjuvant use of palbociclib and endocrine therapy in older patients with high-risk luminal early breast cancer, as an alternative to chemo- and endocrine therapy (NIH, 2026). Another relevant trial is EUROPA, whose interim observations highlights the potential benefits provided by radiotherapy alone instead of endocrine therapy alone, in patients aged 70 years or more with luminal A early breast cancer after breast conserving surgery (Meattini et al., 2025). These studies are opening to a whole new awareness regarding older patients with breast cancer: “Old chemotherapy regimens can maintain their efficacy for the treatment of the most aggressive forms, like the triple-negative tumour, if coupled to anti-HER2 therapies, but in general, their use must be cautiously reconsidered for the other tumour types, and surely not at the same conditions for younger patients”, says Brain, before adding: “The change is also expected to affect the duration of chemotherapy, since the rule of thumb sets this at 6 months, whereas new clinical algorithms suggest that a 3-month threshold should not be trespassed to avoid cellular toxicity, especially with older patients”. The revision of chemotherapy standards, the optimization of endocrine therapy and the assessment of new treatments are gradually reshaping the mindset and approach towards the older patients with early breast cancer, also through the implementation of trial designs, paying closer attention to patients’ conditions and quality of life.

The approach to advanced breast cancer in older patients

The observations made up at this point apply to an even more complex situation when it comes to advanced breast cancer. Prof. Dr. Hans Wildiers, medical oncologist intensely dedicated to geriatric oncology, has placed additional focus on the management of advanced cases of breast cancer. Like his colleagues, he noticed a deep lack of knowledge on the topic since the start of his career, a fact that sounds to him as a great contradiction: “I think there should not be the need for specialised geriatric oncologists,” he begins, “rather, all oncologists should have a solid grounding in geriatric oncology, since most of cancer patients are older people”. His opinion on most of the clinical trials reflects Brain’s thought: “Older individuals, and particularly frail ones, are often excluded from the studies in advance, taking for granted that the outcoming results will be suitable for everyone, without considering the potential higher toxicity of a treatment in a different physiological context”, says Wildiers. Another reason leading to the exclusion of these patients lies in the aggressiveness of standard chemotherapy treatments that would be tested in the control arms of many trials: “This tells enough on the urgent need of new drugs designed specifically for the old and frail population”, he concludes.

Prof. Wildiers then discusses the evolution of endocrine therapy options. Tamoxifen was the first ‘targeted’ endocrine therapy available in breast cancer and proved to effective and feasible in older patients, but it was largely replaced by aromatase inhibitors in the 1990s, because of slightly superior efficacy, although associated with a higher risk of osteoporosis in older people. The last ten years have been characterised by the rising of CDK4/6 inhibitors, like palbociclib, ribociclib and abemaciclib, to be used in combination with aromatase inhibitors for advanced, metastatic or early breast cancer with high-risk of relapse. “All these treatments should require a better assessment of the optimal dosage for older people through specific pharmacokinetics studies,” comments Wildiers, “since the risk of a general overtreatment of these patients is still there”. This is particularly true for very old individuals, for whom a reduced and targeted course of therapy would often be sufficient to ensure a good quality of life for the years ahead, without necessarily resorting to intensive treatment. The phase III SONIA trial is a nice demonstration of the concept that patients not always need ‘the strongest treatment’ first. This study in all age patients (but very relevant for older ones), funded by the Dutch government, focused on luminal advanced breast cancer and enrolled 1050 patients (with a median age of 64 years) between 2017 and 2021, then randomised them to receive endocrine therapy with CDK4/6 inhibitors associated in first-line or second-line setting. It came out that first-line inhibition of CDK4/6 does not add benefits in terms of overall survival, while it can cause more toxicity, a higher financial burden and no improvements in quality of life (Sonke et al., 2024; Wortelboer et al., 2026). The study challenges the assumption of administering the strongest therapies first to all patients with advanced breast cancer as a first-line treatment, suggesting a more individualised approach, which can also mean sparing a patient an unnecessary treatment, whilst achieving the same or better results in terms of quality of life.

It is worth noting there has been research focused also on HER2+ advanced breast cancer. As an example, a phase II trial from the Elderly Task Force and Breast Cancer Group investigated the potential benefits of adding metronomic chemotherapy (thus regularly and at low dosage), in this case oral cyclophosphamide, to pertuzumab and trastuzumab, in metastatic cases of the tumour. The study recruited mainly frail old individuals, showing that the metronomic treatment could provide a better disease control than HER2 dual blockade alone with good tolerance, with the subsequent possibility of superseding the use of more aggressive and extended taxane-based therapies in this population (Wildiers et al., 2018). The conclusions that can be drawn from all the above-mentioned observations point in the direction of a growing attention to the conditions of older patients, bearing in mind a key concept that had also emerged from the Bridging the Age Gap study, and that Prof. Wildiers is keen to emphasise: “With advancing of age and increasing frailties, quality of life is more important than quantity of life. This must be the guiding principle around which new trials are designed” (Morgan et al., 2025).

Conclusion

When talking about breast cancer in older people, the challenge that oncologists have faced in recent decades has been complicated and potentially frustrating: since the available clinical knowledge was generally based on younger cohorts of patients, it was like trying to solve one detective case using evidence from another. There has been a cooperative and international effort to provide new and sound evidence to the field considering all its several aspects and lines of treatment, and the goal has yet to be achieved. Over the years, important institutions like SIOG have committed themselves, if not to drawing up guidelines, then at least to formulating recommendations designed to guide physicians towards a personalised, inclusive approach that focuses on patients’ quality of life, with the help of screening and assessment tools (Biganzoli et al., 2021; Wildiers et al., 2007, 2014).

This gradual shift in mindset represents already an important result, since the previous clinical practices have roots that run deep and are embedded in a much broader scenario: “We live in a society designed for the young and the wealthy,” says provocatively Audisio, “with an ethic that generally doesn’t support old people, especially those who are poor and frail; therefore, the results we have achieved over the years are primarily of an ethical nature, even more so than a therapeutic one”. The continuous presence of inspired oncologists and committed institutions can foster this change, at least at the clinical level. Difficulties will always occur when it comes to decide on a specific treatment for older patients with breast cancer, but thanks to the growing body of scientific evidence, combined with a commitment to caring for and respecting the individual, their conditions and opinions, even more significant results will be achieved, in both the field of oncology and in terms of human dignity.

Acknowledgements

A heartfelt thank you to Riccardo Audisio, Etienne Brain and Hans Wildiers, for their great availability and for their support in getting to know such a complex, interesting and delicate subject.

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