# Homologous recombination deficiency (HRD) in breast cancer

Source: https://onco.cc/terms/hrd-in-breast-cancer/  
OnCo record `hrd-in-breast-cancer` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Homologous recombination deficiency means a tumour cannot mend double-strand DNA breaks properly, most often because BRCA1 or BRCA2 is lost. About seven in ten triple-negative tumours score as deficient, and they respond better to platinum chemotherapy; but unlike ovarian cancer, no breast cancer drug is approved on the basis of an HRD score, only on a germline BRCA result.

## Summary

Three DNA-based measures of genomic instability (loss of heterozygosity, telomeric allelic imbalance and large-scale state transitions) are summed into an HRD score, with deficiency defined as a score of 42 or more or a BRCA1/2 mutation. In three neoadjuvant platinum trials in triple-negative disease, HR deficiency predicted residual cancer burden 0 or I and pathological complete response (odds ratios 4.96 and 6.52 in the platinum, gemcitabine and iniparib trial; 10.18 and 17.00 in two cisplatin trials), remained significant after adjustment for clinical variables, and identified responders among BRCA1/2 non-mutated tumours (Telli 2016). In GeparSixto, HRD was measured in 193 of 315 triple-negative participants: 136 (70.5 percent) were HR deficient, 82 of them (60.3 percent) with a high score but no tumour BRCA mutation; HR deficiency independently predicted pathological complete response (odds ratio 2.60), and adding carboplatin raised the rate from 33.9 to 63.5 percent in HR-deficient tumours but only from 20.0 to 29.6 percent in non-deficient tumours, with the interaction test not significant, so HRD predicted response but not carboplatin benefit; carboplatin improved disease-free survival in triple-negative disease overall (hazard ratio 0.56) (Loibl 2018). Beyond germline BRCA, olaparib produced confirmed responses in metastatic breast cancer with germline PALB2 mutations (objective response 82 percent, median progression-free survival 13.3 months) and somatic BRCA1/2 mutations (50 percent, 6.3 months) but none with ATM or CHEK2 mutations alone (TBCRC 048, Tung 2020). Regulatory use differs from ovarian cancer: NICE's adjuvant olaparib recommendation rests on a germline BRCA mutation (TA886), not an HRD score, and the platinum recommendation in NG101 1.8 applies to all triple-negative disease needing neoadjuvant chemotherapy, HRD-tested or not. The site's general HRD term and the hrd-positive readout carry the ovarian thresholds and assays.

## Fields

- Kind: Term
- Last checked: 2026-09-24
- Also known as: HRD score in breast cancer; HRD in TNBC; Genomic instability score 42; HR-deficient triple-negative breast cancer; BRCAness
- Tags: breast; tnbc

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Homologous_recombination
- Telli, Clin Cancer Res 2016: HRD score predicts response to platinum neoadjuvant chemotherapy in triple-negative breast cancer: https://doi.org/10.1158/1078-0432.ccr-15-2477
- Loibl, Ann Oncol 2018: GeparSixto survival and HRD score as predictor of response: https://doi.org/10.1093/annonc/mdy460
- Tung, J Clin Oncol 2020: TBCRC 048, olaparib for metastatic breast cancer with germline PALB2 or somatic BRCA mutations: https://doi.org/10.1200/jco.20.02151
- NICE TA886: olaparib for adjuvant treatment of BRCA mutation-positive HER2-negative high-risk early breast cancer (May 2023): https://www.nice.org.uk/guidance/ta886
- NICE NG101: early and locally advanced breast cancer (receptor testing 1.3, genetic testing 1.3.6, triple-negative section 1.8): https://www.nice.org.uk/guidance/ng101/chapter/Recommendations

## Connected records

- cancers: [Basal-like 1 triple-negative breast cancer (BL1)](https://onco.cc/cancers/tnbc-basal-like-1/), [BRCA-associated triple-negative breast cancer](https://onco.cc/cancers/brca-associated-tnbc/), [Early triple-negative breast cancer](https://onco.cc/cancers/tnbc-early/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [HRD & BRCA testing](https://onco.cc/technologies/hrd-testing/), [PARP inhibitors](https://onco.cc/technologies/parp-inhibitor/), [Platinum agents](https://onco.cc/technologies/platinum/)
- targets: [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/), [PARP](https://onco.cc/targets/parp/)
- drugs: [Carboplatin](https://onco.cc/drugs/carboplatin/), [Olaparib](https://onco.cc/drugs/olaparib/)
- terms: [Exceptional responder](https://onco.cc/terms/exceptional-responder/), [Germline vs somatic mutations](https://onco.cc/terms/germline-vs-somatic/), [Homologous recombination deficiency (HRD)](https://onco.cc/terms/hrd/), [Pathologic complete response (pCR)](https://onco.cc/terms/pcr/), [Residual cancer burden (RCB)](https://onco.cc/terms/rcb/)
- trials: [GeparSixto](https://onco.cc/trials/geparsixto/)

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