Elsevier

The Lancet

Volume 389, Issue 10074, 18–24 March 2017, Pages 1134-1150
The Lancet

Seminar
Breast cancer

https://doi.org/10.1016/S0140-6736(16)31891-8Get rights and content

Summary

Breast cancer is one of the three most common cancers worldwide. Early breast cancer is considered potentially curable. Therapy has progressed substantially over the past years with a reduction in therapy intensity, both for locoregional and systemic therapy; avoiding overtreatment but also undertreatment has become a major focus. Therapy concepts follow a curative intent and need to be decided in a multidisciplinary setting, taking molecular subtype and locoregional tumour load into account. Primary conventional surgery is not the optimal choice for all patients any more. In triple-negative and HER2-positive early breast cancer, neoadjuvant therapy has become a commonly used option. Depending on clinical tumour subtype, therapeutic backbones include endocrine therapy, anti-HER2 targeting, and chemotherapy. In metastatic breast cancer, therapy goals are prolongation of survival and maintaining quality of life. Advances in endocrine therapies and combinations, as well as targeting of HER2, and the promise of newer targeted therapies make the prospect of long-term disease control in metastatic breast cancer an increasing reality.

Section snippets

Breast cancer: epidemiology

Breast cancer is the most common malignancy in women, and one of the three most common cancers worldwide, along with lung and colon cancer. In 2012, almost 1·7 million people were diagnosed worldwide and about half a million people died from this disease.1, 2 One in eight to ten women will get breast cancer during their lifetime. Mortality from breast cancer in North America and the European Union (EU) has decreased, and this decrease is mostly attributable to early detection and efficient

Early breast cancer: treatment concepts and biology

Early breast cancer without detectable distant metastases is a potentially curable disease. After diagnosis, therapy concepts need to be decided in a multidisciplinary team meeting (tumour board). Primary surgery and removal of the tumour might not be the best option for every patient even though this could be the patient's initial logical request. Yet, for certain biological tumour subtypes such as triple-negative breast cancer or HER2-positive disease, primary systemic therapy could be better

Surgery

Breast conservation is established as the intended surgical standard of care for most clinical situations in breast cancer.15 Developments in surgical techniques (oncoplastic procedures)16 and multidisciplinary approaches (primary systemic therapy), as well as increased treatment of patients in dedicated and certified breast units, have improved women's access to this organ-saving surgical approach.17

While the overarching principle of achieving clear margins remains the surgical standard of

Indication for systemic therapy

The most frequent tumour biology is HER2-negative luminal tumours (around 70%) in which the indication for neoadjuvant or adjuvant chemotherapy depends on further criteria such as proliferation, tumour grade, or lymph node involvement. Since only a few breast cancer centres routinely determine molecular subtype by a multigene assay, immunohistochemistry is mostly used to distinguish luminal A biology from luminal B. Yet, in tumours that are hormone-receptor positive with an intermediate Ki67

Early breast cancer: special situations

Evidence is scarce on special situations in early breast cancer, such as age extremes or patients who are pregnant. Generally, therapy of young and elderly patients with breast cancer should not deviate from standard management unless individualisation is required because of comorbidities and personal situations.

For young patients (<40 years), who represent less than 7% of all patients in high-income countries, a biannual international consensus conference (breast cancer in young women [BCY])

Metastatic breast cancer: therapy concepts

In contrast with early breast cancer, metastatic breast cancer is considered incurable with currently available therapies. Based on data from 1996, long-term survivors do exist but are very rare—ie, less than 5%.161 Whether and how this percentage will change with current therapies that have shown an overall survival advantage is still unknown.

Nowadays, patients with metastatic breast cancer differ substantially from patients 10–20 years ago and are much more difficult to treat because they

Endocrine-responsive metastatic breast cancer

International guidelines recommend endocrine therapy as the first therapeutic choice in patients with HER2-negative luminal metastatic breast cancer unless visceral crisis or another life-threatening situation requires chemotherapy.164 Endocrine therapy is usually feasible if symptoms allow a wait of about 3–4 months until best response. Endocrine drugs for metastatic breast cancer include tamoxifen, aromatase inhibitors, fulvestrant, and progestins. These drugs are ideally given sequentially,

Management of HER2-positive metastatic breast cancer

Anti-HER2 therapy is recommended as early as possible in patients with HER2-positive metastatic breast cancer. Even though efficacy of trastuzumab or lapatinib together with endocrine therapy (aromatase inhibitor) was shown in several phase 2–3 trials for postmenopausal patients174 and led to registration of these combinations, combination with chemotherapy is currently recommended in early lines of therapy because of the overall survival advantage.

Based on the pivotal data,175 trastuzumab plus

Chemotherapy for metastatic breast cancer

Chemotherapy is always indicated in triple-negative breast cancer after endocrine options have been exhausted in luminal disease or if rapid response is needed in life-threating situations or in patients who are highly symptomatic. Unless patient symptoms require a combination chemotherapy, sequential mono-chemotherapies are recommended, as combination chemotherapy does not prolong survival.181 Mono-chemotherapy can be given until progression or intolerable toxic effects, whereas because of

Future perspectives for metastatic breast cancer

Next-generation sequencing and mutation analysis have transformed management of other solid tumours, but not yet those of patients with metastatic breast cancer. So far, the only clinically relevant biomarkers and validated therapeutic targets in metastatic breast cancer are ER, PgR, and HER2. Nevertheless, metastatic breast cancer is heterogeneous and several clinically potentially relevant mutations have been identified. Yet, personalised approaches are currently only available for a few

Search strategy and selection criteria

We searched MEDLINE between June 16, 2015, and June 19, 2016 with no language restrictions. We used the search terms “breast cancer” in combination with specific terms covering the different steps of diagnosis and treatment as appropriate. We largely selected publications in the past 5 years, but did not exclude commonly referenced and highly regarded older publications. We also searched the reference lists of articles identified by this search strategy and selected those we judged relevant.

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