Treatment Strategies for Triple-Negative Breast Cancer in Older Women: What a Major Review Found

Table of Contents

• Key Points
• Background: Why This Research Matters
• What Is Triple-Negative Breast Cancer?
• How the Research Was Conducted
• Quality Assessment of Included Studies
• Key Findings: Surgery
• Key Findings: Postoperative Radiation Therapy
• Key Findings: Systemic Therapy
• Key Findings: Age Comparisons and Outcomes
• Clinical Implications: What This Means for Patients
• Limitations: What the Study Could Not Prove
• Recommendations for Patients and Families
• Frequently Asked Questions
• Source Information

Key Points

• In two SEER studies of about 18,000 older women, breast-conserving surgery plus radiation was associated with better overall and breast cancer-specific survival than mastectomy.
• In one SEER study, 5-year cumulative death incidence was 8.35% after breast-conserving surgery plus radiation versus 18.56% after mastectomy.
• Omitting radiation after breast-conserving surgery was correlated with worse outcomes and a doubling in future mastectomy rates due to locoregional recurrence.
• Eleven retrospective studies of over 57,000 patients aged 65+ found adjuvant systemic therapy associated with improved outcomes; in one of them (Guo et al.), breast cancer-specific survival benefits were not seen in T1a/b tumors or in patients over 80, although overall survival still improved in patients over 80.
• The review concluded treatment decisions should be based on tumor biology rather than age alone, using a multidisciplinary, patient-centered approach.

Background: Why This Research Matters

Globally, more than 30% of breast cancer cases occur in women older than 70 years of age. Triple-negative breast cancer accounts for approximately 15% of all breast cancer cases. The relative proportion of triple-negative breast cancer decreases with age, but the actual number of older women with this cancer is rising. This rise is due to an aging population.

Older patients are often excluded from randomized controlled trials because of age restrictions. This exclusion makes it difficult to collect robust data on how best to treat them. The authors of this review note that future randomized controlled trials involving this population are unlikely in the near term. This systematic review aims to fill that gap by synthesizing real-world treatment patterns and outcomes.

The review explores differences in treatment receipt and survival outcomes across three key dimensions:

• Age (older patients compared with younger patients)
• Treatment intensity (treated compared with untreated)
• Treatment type

The authors focused on the potentially curable nature of early-stage triple-negative breast cancer. They wanted to understand whether age affects therapy and outcomes in older women.

What Is Triple-Negative Breast Cancer?

Triple-negative breast cancer is a heterogeneous subtype. Heterogeneous means the tumors are not all the same. This subtype is characterized by the absence of three receptors: estrogen receptor, progesterone receptor, and ERBB2 (formerly known as HER2) receptor expression. Because these three receptors are absent, treatments that target them, such as hormone therapy or HER2-targeted drugs, do not work for this cancer type.

Triple-negative breast cancer is often linked to a poorer prognosis. It is more prevalent among African American women, younger individuals, and tumors of higher grade and stage. The most common histological subtype is infiltrating ductal carcinoma of no special type. This is followed by metaplastic and pleomorphic invasive lobular carcinoma.

Rare subtypes account for less than 2% of cases. These rare subtypes are generally well-differentiated, low-grade tumors. They are more frequently observed in older patients compared with the no special type category. These rarer triple-negative breast cancer subtypes include:

• Low-grade adenosquamous carcinoma
• Fibromatosis-like spindle cell carcinoma
• Salivary gland-like tumors (adenoid cystic and mucoepidermoid carcinoma)
• Apocrine carcinoma
• Secretory carcinoma

Distant recurrence in triple-negative breast cancer peaks approximately 3 years after diagnosis. These recurrences often involve visceral organs. In addition, 11.5% to 14% of de novo metastatic triple-negative breast cancer cases present with brain metastases. De novo means the cancer was already metastatic at the time of first diagnosis. Distant recurrences substantially reduce survival. They necessitate more aggressive and expedited treatment approaches, including for older women, because these recurrences directly affect lifespan.

The standard of care for early breast cancer includes local control through breast-conserving surgery with postoperative radiation therapy or mastectomy with or without radiation therapy. This is combined with or without systemic therapy. For triple-negative breast cancer, primary systemic therapy (also called neoadjuvant systemic therapy) is recommended for T2N0 or any TN1+ disease and above. This therapy typically involves cytotoxic regimens, such as sequential anthracycline-based and taxane-based systemic therapy.

Recent evidence supports the integration of platinum-based agents in the primary systemic therapy setting. This is particularly to enhance pathologic complete response rates. Pathologic complete response means no cancer cells are found in the tissue removed during surgery. Trials such as CALGB 40603 (Alliance) and GeparSixto demonstrated improved pathologic complete response rates by adding carboplatin to triple-negative breast cancer regimes. This approach is increasingly adopted in clinical practice for appropriately selected older patients.

Recently, immune checkpoint inhibitors, such as pembrolizumab, have been introduced for primary systemic and adjuvant settings. Adjuvant means treatment given after the main treatment to reduce the risk of cancer returning. Poly(ADP-ribose) polymerase (PARP) inhibitors such as olaparib have shown efficacy in the primary systemic therapy or adjuvant setting for patients with germline BRCA mutations. Germline means the mutation is inherited. These agents, however, are not approved for routine use in the primary systemic therapy setting.

Systemic therapy can lead to toxicity that may be less tolerable in older women. This toxicity can substantially impair quality of life due to comorbidities, polypharmacy, and frailty. Comorbidities are other medical conditions a patient has at the same time. Polypharmacy means taking multiple medications. Frailty means a state of increased vulnerability to stressors due to reduced physiological reserve.

The use of primary systemic therapy and breast-conserving surgery for triple-negative breast cancer decreases with age. This decrease occurs even after accounting for cancer stage and comorbidities. Appropriate use of therapies may be influenced by clinicians' erroneous subjective frailty assessments. This highlights the need for objective frailty measurement tools. Integrating these tools with other relevant factors ensures that treatment decisions prioritize the disease's biological characteristics.

How the Research Was Conducted

This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The authors developed inclusion and exclusion criteria using the population, intervention, comparison, outcomes framework.

The population was women with triple-negative breast cancer as the subtype, aged 70 years or older, per the International Society of Geriatric Oncology (SIOG) definition. Given the variability in defining older, studies defining this population as 65 years of age and older were also included.

The intervention was patients who underwent or were given the option of surgery, postoperative radiation therapy, or systemic therapy. The comparison was other therapeutic options, younger patients, or no treatment. The outcomes were any metric assessing one or more outcomes, including cancer-specific outcomes (disease-free survival or recurrence), toxicity, or survival (breast cancer-specific or overall).

The search was limited to English-language studies. Exclusion criteria included case reports, studies involving male patients (due to limited literature), and papers on preidentified genetic abnormalities.

Medical Subject Headings (MeSH) terms and free-text keywords were used to search five databases: MEDLINE, Embase, PubMed, Web of Science, and Scopus. The authors searched these databases for publications from the last decade (2014-2023). This timeframe was chosen to align with recent advancements in treating patients regardless of age and updated treatment guidelines. In addition, the authors manually searched reference lists of papers identified during abstract screening for relevant studies.

Two reviewers independently screened studies for eligibility and extracted data. Any discrepancies were resolved through discussion between the reviewers. If no consensus was reached, a third independent reviewer was consulted.

The extracted data included study identifiers: authors, year, country, study type, and data source. The extracted data also included population characteristics: age range and number of patients. The extracted data also included tumor features: stage, grade, and receptor status. The extracted data also included treatment modalities evaluated: surgery, radiation therapy, and systemic therapy. The extracted data also included outcome measures: overall survival, breast cancer-specific survival, disease-free survival, recurrence, and toxicity. The authors also recorded author-reported study limitations as part of quality appraisal.

The search, conducted in December 2023, identified 10,807 records. After duplicates were removed, 7,171 records remained. Following PRISMA screening guidelines, the title and abstract review reduced this number to 37 reports that met the inclusion criteria. However, 8 reports were excluded because only the abstracts were published. Reasons for exclusion during full-text screening included insufficient specificity for triple-negative breast cancer or inadequate age stratification (for example, defining older as 50 years and older).

The search did not yield randomized controlled trials. Most included studies were retrospective cohort studies conducted in the United States, Asia, and the United Kingdom. A retrospective cohort study looks back at existing data to examine outcomes.

Quality Assessment of Included Studies

Risk of bias was assessed using the Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool. Most studies were retrospective and rated as having a moderate overall risk of bias. Common concerns included confounding and selection bias. Confounding means that other factors could explain the results. Selection bias means that the groups being compared may differ in important ways. These biases were mainly due to unmeasured factors such as frailty and comorbidities.

Bias related to intervention classification, missing data, and outcome measurement was generally low. A few studies showed moderate concerns in these domains. Selective reporting was rated moderate in most studies.

Key Findings: Surgery

The surgical literature on triple-negative breast cancer compares breast-conserving surgery plus radiation therapy and mastectomy with or without radiation therapy across various age groups. Three studies addressed this topic. Two were based on the US Surveillance, Epidemiology, and End Results (SEER) Program cohort studies. One was from an institutional database in China.

The SEER study by Mburu et al. used inverse probability treatment weighting to investigate outcomes in older women with triple-negative breast cancer older than 66 years of age. Their analysis revealed the lowest cumulative incidence of death in patients undergoing breast-conserving surgery plus radiation therapy. This was particularly true among women older than 75 years of age. These findings persisted after multivariate analysis and adjustments for systemic therapy. Improved overall survival and breast cancer-specific survival were observed in patients with stage III tumors undergoing breast-conserving surgery plus radiation therapy.

The specific 5-year cumulative death incidences reported in the Mburu et al. study were:

• Breast-conserving surgery plus radiation therapy: 8.35%
• Mastectomy: 18.56%
• Mastectomy plus radiation therapy: 36.02%
• Breast-conserving surgery alone: 20.44%

The second SEER study employed propensity matching and focused on older women. The second SEER study also demonstrated improved 5-year overall survival and breast cancer-specific survival. This improvement was for patients undergoing breast-conserving surgery plus radiation therapy. This improvement was compared with patients treated with mastectomy alone. It is important to note that both SEER studies, with a combined sample size of 18,000, covered overlapping periods. This raises potential concerns about data duplication.

In contrast, the study by Zhong et al. compared mastectomy with axillary lymph node dissection with breast-conserving surgery without axillary lymph node dissection, sentinel lymph node biopsy, or radiation therapy. They observed no statistically significant differences in disease-free survival between these surgical approaches. The study noted higher rates of ipsilateral breast cancer recurrence in patients treated with breast-conserving surgery without radiation therapy, however, particularly for triple-negative breast cancer, compared with luminal subtypes. Ipsilateral means on the same side. Notably, this study did not exclusively focus on triple-negative breast cancer and did not adjust for the impact of systemic therapy. This indicates that some patients undergoing breast-conserving surgery may have also received systemic therapy.

These findings align with the observation by Mburu et al. that survival rates were lower in patients undergoing breast-conserving surgery without radiation therapy than in patients undergoing mastectomy alone. This may be due to increased local recurrence rates.

Importantly, these observations do not necessarily extend to younger age groups. In a cohort of patients younger than 60 years of age, similar outcomes in terms of breast cancer-specific survival and overall survival were observed between breast-conserving surgery and mastectomy.

Key Findings: Postoperative Radiation Therapy

Eight retrospective cohort studies evaluated the role of postoperative radiation therapy in older women with triple-negative breast cancer. These studies included work based on SEER and the US National Cancer Database registries. They looked at outcomes following breast-conserving surgery, mastectomy, or both. Two pairs of studies used identical study periods (2004-2015). Another study used data from hospitals in Hong Kong, Malaysia, and Singapore between 2006 and 2012.

Where reported, radiation therapy in the included studies primarily referred to whole-breast irradiation following breast-conserving surgery. Some studies, however, also included postmastectomy radiation therapy, especially in node-positive disease. Not all studies clearly specified target volumes such as chest wall. Not all studies clearly specified regional node levels with or without internal mammary. Not all studies clearly specified whether a boost was applied, for example a tumor bed boost or a scar boost. Not all studies clearly specified dose and fractionation. All these factors are known to be significant for outcomes, including breast cancer outcomes and toxicity.

Six of these studies reported improvements in overall survival and breast cancer-specific survival. For instance, Tang et al. saw age and radiation therapy as independent prognostic factors for overall survival. They also demonstrated radiation therapy's role in improving breast cancer-specific survival.

Xu et al. developed a nomogram to stratify older women with triple-negative breast cancer by radiation therapy risk. A nomogram is a visual tool that predicts risk based on multiple factors. Their findings suggested overall survival and breast cancer-specific survival benefits in high-risk patients. They found overall survival benefits only in intermediate-risk groups. They observed no benefits in low-risk patients. Risk groups were defined based on a numerical categorization of age, race, ERBB2 status, T stage, and N stage. These findings underscore the importance of tailoring radiation therapy recommendations to individual risk profiles.

Age-related disparities in treatment were also noted. Radiation therapy was more frequently withheld in older women with triple-negative breast cancer who have more comorbidities or following systemic therapy. Even after propensity score matching, radiation therapy omission was an independent factor correlated with poorer overall survival. In addition, breast-conserving surgery without radiation therapy saw a doubling in future mastectomy rates due to locoregional recurrence. Locoregional means in the same area as the original cancer.

Older patients were more likely to accept postoperative radiation therapy than systemic therapy. This factor could partially rationalize the observed changes in overall survival.

One study that had a smaller sample size (n=1,138) observed no survival benefit from radiation therapy in older women with triple-negative breast cancer. Differences in findings could be attributed to limited statistical power, variations in tumor subtypes, or regional differences in treatment regimens.

Key Findings: Systemic Therapy

Eleven retrospective cohort studies explored the associations between systemic therapy and outcomes in older women with triple-negative breast cancer. Collectively, these studies included more than 57,000 patients aged 65 years and older. Potential data duplication is possible due to six studies using the SEER database and potential overlap with the National Cancer Database. Most research focused on adjuvant systemic therapy, with only one study investigating neoadjuvant therapy.

All included studies demonstrated associations between adjuvant systemic therapy and improved outcomes. Four studies identified better overall survival. Two also reported improvements in breast cancer-specific survival. These observations persisted even after propensity score matching. Tang et al. saw systemic therapy receipt as an independent favorable prognostic factor for overall survival.

Systemic therapy regimens varied by age. Younger patients (younger than 70 years) were more likely to receive anthracycline and taxane-based regimens. Older patients (70 years and older) more often received carboplatin-based regimens. No substantial differences were observed in recurrence-free survival or breast cancer-specific survival between regimens within age groups.

Schreiber et al. reported that patients 76 years of age and older were less likely to receive anthracycline and taxane-based regimens. This was likely due to concerns about treatment toxicity.

Reduced systemic therapy use was independently associated with increased age and comorbidities. This may reflect higher hospitalization risks during and after treatment. Guo et al. found improvements in overall survival and breast cancer-specific survival with adjuvant systemic therapy in older women with triple-negative breast cancer. However, breast cancer-specific survival benefits were not observed in early-stage tumors (T1a/b) or in patients older than 80 years of age.

Key Findings: Age Comparisons and Outcomes

Overall, outcomes did not show significant differences between women aged 70 years and older and women younger than 70 years at a median follow-up of 46 months. Median follow-up means half the patients were followed for longer than this time and half for less.

Older women with triple-negative breast cancer exhibited less aggressive features. These features included lower Ki67, higher androgen receptor, and higher Bcl2 expression. Ki67 is a marker of how fast cancer cells are dividing. Lower Ki67 means slower cell division. Higher androgen receptor and Bcl2 expression are also associated with less aggressive tumor behavior.

The authors noted that the lack of overall outcome improvements for older women with triple-negative breast cancer following treatment may not solely be due to absent targetable receptors. The intrinsic biology in older patients may be relatively favorable. Instead, treatment selection biases against active treatment due to age-related factors may contribute substantially.

Clinical Implications: What This Means for Patients

This review has several important implications for older women with triple-negative breast cancer and their care teams.

First, breast-conserving surgery plus radiation therapy was associated with improved overall survival and breast cancer-specific survival compared with mastectomy with or without radiation therapy. The Mburu et al. study found that the 5-year cumulative death incidence was 8.35% for breast-conserving surgery plus radiation therapy, compared with 18.56% for mastectomy and 36.02% for mastectomy plus radiation therapy. This suggests that breast-conserving surgery followed by radiation therapy may be the preferred approach for many older women with early-stage triple-negative breast cancer.

Second, the lack of radiation therapy after breast-conserving surgery was correlated with worse outcomes. The Mburu et al. study found that breast-conserving surgery alone had a 5-year cumulative death incidence of 20.44%, compared with 8.35% for breast-conserving surgery plus radiation therapy. In addition, breast-conserving surgery without radiation therapy saw a doubling in future mastectomy rates due to locoregional recurrence.

Third, systemic therapy was associated with improved outcomes in older women with triple-negative breast cancer. All included studies demonstrated associations between adjuvant systemic therapy and improved outcomes. However, the benefits were not observed in early-stage tumors (T1a/b) or in patients older than 80 years of age.

Fourth, older women with triple-negative breast cancer were more likely to receive radiation therapy than systemic therapy. The lack of radiation therapy correlated with worse outcomes. This finding suggests that radiation therapy may be underutilized in this population.

Fifth, treatment decisions should be biology based and guided by a multidisciplinary, holistic, and patient-centered approach. This approach should carefully consider comorbidities, functional status, social support, and patient preferences. The authors emphasize that age alone should not determine treatment. Instead, the tumor's biological characteristics and the patient's overall health should guide decisions.

The authors also note that appropriate use of therapies may be influenced by clinicians' erroneous subjective frailty assessments. This highlights the need for objective frailty measurement tools. Integrating these tools with other relevant factors ensures that treatment decisions prioritize the disease's biological characteristics.

Limitations: What the Study Could Not Prove

This systematic review has several limitations that patients and clinicians should consider.

First, the search did not yield randomized controlled trials. Most included studies were retrospective cohort studies. Retrospective studies look back at existing data. They cannot prove cause and effect. They can only show associations.

Second, most studies were rated as having a moderate overall risk of bias. Common concerns included confounding and selection bias. Confounding means that other factors could explain the results. Selection bias means that the groups being compared may differ in important ways. These biases were mainly due to unmeasured factors such as frailty and comorbidities.

Third, potential data duplication is possible. Six studies used the SEER database, and there was potential overlap with the National Cancer Database. Two SEER studies, with a combined sample size of 18,000, covered overlapping periods. This raises concerns about data duplication.

Fourth, not all studies clearly specified radiation therapy target volumes, whether a boost was applied, or dose and fractionation. All these factors are known to be significant for outcomes, including breast cancer outcomes and toxicity.

Fifth, the study by Zhong et al. did not exclusively focus on triple-negative breast cancer and did not adjust for the impact of systemic therapy. This indicates that some patients undergoing breast-conserving surgery may have also received systemic therapy.

Sixth, one study that had a smaller sample size (n=1,138) observed no survival benefit from radiation therapy in older women with triple-negative breast cancer. Differences in findings could be attributed to limited statistical power, variations in tumor subtypes, or regional differences in treatment regimens.

Seventh, the review was limited to English-language studies. This may introduce language bias.

Eighth, the review excluded case reports and studies involving male patients. This limits the generalizability of the findings.

Recommendations for Patients and Families

Based on this review, older women with triple-negative breast cancer and their families should consider the following:

1. Discuss the full range of treatment options with your care team. This includes breast-conserving surgery plus radiation therapy, mastectomy with or without radiation therapy, and systemic therapy.
2. Ask about the potential benefits and risks of each treatment option. The review found that breast-conserving surgery plus radiation therapy was associated with improved overall survival and breast cancer-specific survival compared with mastectomy.
3. Discuss the role of radiation therapy after breast-conserving surgery. The review found that the lack of radiation therapy correlated with worse outcomes.
4. Ask about systemic therapy options. The review found that systemic therapy was associated with improved outcomes in older women with triple-negative breast cancer. However, the benefits were not observed in early-stage tumors (T1a/b) or in patients older than 80 years of age.
5. Request an objective assessment of your overall health, including comorbidities, functional status, and frailty. The authors emphasize that treatment decisions should be biology based and guided by a multidisciplinary, holistic, and patient-centered approach.
6. Discuss your social support and personal preferences with your care team. These factors should be carefully considered in treatment decisions.
7. Ask whether a multidisciplinary team is involved in your care. The authors recommend a multidisciplinary approach that includes input from surgeons, radiation oncologists, medical oncologists, and geriatric specialists.

The authors conclude that treatment decisions should be biology based and guided by a multidisciplinary, holistic, and patient-centered approach. This approach should carefully consider comorbidities, functional status, social support, and patient preferences. Age alone should not determine treatment.

Frequently Asked Questions

I am 78 and just diagnosed with early-stage triple-negative breast cancer. Does my age mean I should get less treatment?

The review concluded that treatment decisions should be based on tumor biology rather than age alone. It found older women often have more favorable tumor biology yet receive less aggressive treatment. Decisions should involve a multidisciplinary, patient-centered approach considering comorbidities, functional status, social support, and your preferences. Ask your care team for an objective frailty assessment.

What surgery options does the review describe for older women with early-stage triple-negative breast cancer?

The review compared breast-conserving surgery plus radiation therapy with mastectomy, with or without radiation therapy. In two SEER studies of about 18,000 women, breast-conserving surgery plus radiation was associated with better overall and breast cancer-specific survival than mastectomy. One smaller study found no significant disease-free survival difference between certain surgical approaches, but it did not focus only on triple-negative breast cancer.

What does the 8.35% versus 18.56% death incidence mean for me?

In one SEER study of older women with triple-negative breast cancer, the 5-year cumulative incidence of death was 8.35% after breast-conserving surgery plus radiation therapy, compared with 18.56% after mastectomy. These are group averages from that study, not individual predictions. Your own risk depends on your tumor stage, biology, overall health, and the treatment you receive.

Is radiation therapy necessary after breast-conserving surgery?

The review found that omitting radiation after breast-conserving surgery was correlated with worse outcomes. In one SEER study, breast-conserving surgery alone had a 5-year cumulative death incidence of 20.44%, compared with 8.35% with radiation. Omitting radiation was also linked to a doubling in future mastectomy rates due to locoregional recurrence. Discuss the role of radiation with your care team.

Does systemic therapy help older women with triple-negative breast cancer?

Eleven retrospective cohort studies including more than 57,000 patients aged 65 and older found associations between adjuvant systemic therapy and improved outcomes. However, breast cancer-specific survival benefits were not observed in early-stage T1a/b tumors or in patients older than 80 years. Systemic therapy can cause toxicity that may be less tolerable in older women with comorbidities, polypharmacy, or frailty.

What are the risks of systemic therapy for older women?

The review notes that systemic therapy can lead to toxicity that may be less tolerable in older women. This toxicity can substantially impair quality of life due to comorbidities, polypharmacy, and frailty. Reduced systemic therapy use was independently associated with increased age and comorbidities, possibly reflecting higher hospitalization risks during and after treatment. Discuss potential benefits and risks with your care team.

Should I ask for a frailty assessment before deciding on treatment?

Yes. The review states that appropriate use of therapies may be influenced by clinicians' erroneous subjective frailty assessments. It highlights the need for objective frailty measurement tools. Integrating these tools with other relevant factors ensures that treatment decisions prioritize the disease's biological characteristics. Ask your care team for an objective assessment of your overall health, including comorbidities, functional status, and frailty.

I'm 74 and just diagnosed with early-stage triple-negative breast cancer — should I get a second opinion before agreeing to surgery?

A second opinion can help confirm whether breast-conserving surgery plus radiation therapy is appropriate for you, since that approach was associated with better overall and breast cancer-specific survival than mastectomy in older women. It can also clarify whether radiation after breast-conserving surgery is being included, because omitting it correlated with worse outcomes. Because treatment decisions should be based on tumor biology rather than age alone, an independent review of your pathology and health status can support a multidisciplinary, patient-centered plan. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

Original article title: Treatment strategies for triple-negative primary breast cancer in older women: a systematic review.

Authors: Buraq Ahmed, BA; Qutaiba Al-Khames Aga, PhD; Kwok-Leung Cheung, DM, FACS; Jana de Boniface, MD, PhD; Michael Gnant, MD; Maria-Joao Cardoso, MD, PhD; Emad Rakha, PhD; Thiraviyam Elumalai, MD; Nadia Harbeck, MD, PhD; Orit Kaidar-Person, MD, PhD; Amit Agrawal, MS, DM

Publication: JNCI Cancer Spectrum, 2025, Volume 9, Issue 3, pkaf049

DOI: https://doi.org/10.1093/jncics/pkaf049

Advance Access Publication Date: May 15, 2025

Author affiliations: University of Cambridge, Cambridge, United Kingdom; Cambridge University Hospitals, Cambridge, United Kingdom; University of Waterloo, Waterloo, Canada; University of Nottingham, Derby, United Kingdom; Karolinska Institutet, Stockholm, Sweden; Capio St Göran's Hospital, Stockholm, Sweden; Medical University of Vienna, Vienna, Austria; Austrian Breast & Colorectal Cancer Study Group, Vienna, Austria; Champalimaud Foundation and Lisbon University Faculty of Medicine, Lisbon, Portugal; Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom; LMU University Hospital, Munich, Germany; Sheba Tel Hashomer, Ramat Gan, Israel; Tel Aviv University, Tel Aviv, Israel

Corresponding author: Amit Agrawal, MS, DM, FRCS, Cambridge University Hospitals, Hills Rd, Cambridge CB2 0QQ, United Kingdom

Note: This patient-friendly article is based on peer-reviewed research. The original article is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.