Breast Cancer Treatment
Once a woman has received the news of a confirmed early breast cancer diagnosis, she will begin the path towards treatment.
Approaches vary according to tumour location, size and characteristics, which also vary widely from woman to woman.
The common factor should be that any approach to therapy should follow the highest recognised standards and guidelines.
This includes continuous assessment by a multidisciplinary team working within specialist breast cancer services that care for a high volume of breast cancer patients because this has been demonstrated to improve disease outcomes and quality of life.
Women should be appropriately informed about the risks and benefits of any therapy and have all their concerns addressed regarding aspects such as recovery, side effects, fertility and sexuality.
They should also receive psycho-oncological support throughout this process if they so wish.
What Happens After a Breast Cancer Diagnosis
The diagnostic process itself, including imaging and biopsies for example, help in determining tumour characteristics that will be used to guide treatment. Tumours are graded based on the size, the presence of tumour markers such as hormone receptors, HER2, a proliferation marker Ki67, and genomic molecular signature, if available (see the Genetic and Genomic Testing section).
The cancer will also be staged according to its invasiveness (see the Pathology section below). Based on these factors, the treatment pathway can involve surgery (with assessment of lymph node status to see if the cancer has spread), systemic therapy before (neoadjuvant) and/or after (adjuvant) surgery, and radiotherapy. The approach should be based on a decision by the multidisciplinary team and the woman concerned. Premenopausal women should be informed about effects that some hormone therapy and chemotherapy may have on their future ability to get pregnant and discuss options to preserve their fertility.
Any breast surgery should be performed by an experienced breast surgeon who meets the standards set by European Breast Surgical Oncology Certification (BRESO) and the ECIBC Breast Cancer Service Requirements.
The surgeon is a lead member of the multidisciplinary team. A list of certified surgeons is available on the BRESO website. When planning for surgery, clip-marking is used. It a technique where a small, 2-3 mm device of is placed in the breast tissue to indicate where the surgical excision needs to be made. The European Breast Cancer Guidelines recommend that the clip be placed at the time of biopsy. This avoids the need for an additional procedure to insert it before surgery.
Sentinel lymph node biopsy (SLNB) is usually performed during the surgery to remove the primary tumour but can be performed before or afterward. This process uses a radioactive substance or blue dye to locate the first lymph nodes to which a tumour is likely to spread. These nodes are then removed and examined by the pathologist for cancer cells as a sign of the tumour having spread beyond the breast. Removing sentinel lymph nodes is preferable to removal of all lymph nodes in order to reduce the occurrence of lymphoedema (chronic swelling of the arm).
Depending on the tumour size and characteristics, a woman may be offered breast-conserving surgery (BCS) or mastectomy. With BCS (also known as lumpectomy), just the tumour and surrounding area are removed in order to maintain the integrity and appearance of the breast. This is recommended only for lower grade cancers, usually in combination with radiotherapy.
When a tumour is larger or more invasive, a mastectomy can be performed to remove the whole breast. Depending on the degree of invasiveness, this may also involve axillary lymph node dissection (removing the lymph nodes in the underarm area), or removing some of the muscles in the chest wall. Partial mastectomy is another approach for lower grade tumours. Nipple-sparing mastectomy removes the breast tissue while maintaining the nipple.
This is particularly useful for breast reconstruction, where the breast is surgically rebuilt and an artificial implant is inserted. This procedure should be performed at the time of the primary surgery or up to 1 year afterwards, as stated in the ECIBC Manual for Breast Cancer Services. This procedure should be offered and covered by the national health system.
After surgery, the removed lymph nodes and breast tissue undergo pathology testing to provide information about the tumour that will be essential for later (adjuvant) treatment decisions.
The Pathology Report
Women should receive a copy of their pathology report describing the tumour characteristics based on the biopsy, and evaluation of tissue removed at surgery. It includes the tumour subtype and stage, size and various prognostic factors.
The most important prognostic factors in early breast cancer are the expression of oestrogen (ER) and progesterone (PgR) receptors, HER2, proliferation markers such as Ki67, the number of regional lymph nodes involved, tumour histology, the size, grade and the presence of tumour cells in the vascular tissue surrounding the tumour area. The presence of clear margins, with no tumour cells in the area surrounding the removed tumour tissue, is also very important.
Breast cancer has the following molecular subtypes which help determine treatment choice:
- Luminal A-like: ER and PgR positive, HER2 negative, and low Ki67
- Luminal B-like (HER2 negative): ER positive, HER2 negative, and either high Ki67 or low PgR, plus a high-risk molecular signature, if available
- Luminal B-like (HER2 positive): ER positive, HER2 positive, and any Ki67 or PgR level
- HER2: HER2 positive and ER and PgR absent
- Basal like/triple negative: HER2 negative and ER and PgR absent
Tumour grade is a score calculated based on the appearance of tumour cells and is ranked from Grade 1 to Grade 3, from low to higher risk.
Tumour stage is determined by the size of the tumour and if it has spread beyond the breast. There are four stages usually expressed as I to IV, from least invasive to advanced/metastatic.
Radiotherapy (RT) of the whole breast after breast-conserving surgery is strongly recommended because it reduces the risk of recurrence.
RT after mastectomy in women with positive lymph nodes also reduces the risk of recurrence and mortality. RT can be given after immediate breast reconstruction. ECIBC Breast Cancer Service Requirements indicate that the time between surgery and/or systemic treatment and RT should not exceed 8 weeks.
The most common type of RT uses a large machine to deliver radiation to the affected area to damage and kill cancer cells. It also affects healthy cells. The most common side effects are fatigue, and skin irritation or swelling in the treated area. RT is generally administered 5 days a week for 3 weeks, depending on the tumour characteristics. Other forms of RT such as partial breast radiation are also in use.
In cases of hormone-positive tumours (ER+ and/or PgR+, ie, all luminal-like cancers), women should be offered hormone therapy that limits or blocks the amount of oestrogen in the body because this hormone makes the tumours grow. Examples of hormone therapies (or endocrine therapy) are tamoxifen and aromatase inhibitors.
In premenopausal women, 5 to 10 years of tamoxifen therapy is considered standard of care. In women with higher risk of recurrence, an aromatase inhibitor can be used; however, because these do not stop the ovaries from making oestrogen, ovarian function must be suppressed with other medications.
Postmenopausal women can use aromatase inhibitors or tamoxifen. An aromatase inhibitor can be used from the start, or after 2 or 3 years on tamoxifen, or as extended therapy after 5 years on tamoxifen. Hormone therapy can also be started before surgery (ie, neoadjuvant).
Tamoxifen is associated with an increased risk for thromboembolic complications and endometrial hyperplasia, so women with risk factors for these complications should discuss this with their doctor. Aromatase inhibitors are associated with bone and joint pain, and increased risk of osteoporosis.
In hormone-positive breast cancer, hormone therapy has been shown to reduce the risk for recurrence and to increase survival compared with no hormonal therapy.
Some tumours overexpress HER2, and a specific treatment called trastuzumab blocks the HER2 receptors and stops HER2-associated tumour growth. This treatment is administered intravenously. It is used in people with HER2-positive tumours, commonly in combination with chemotherapy. Side effects of anti-HER2 therapy include headaches, nausea, or heart problems.
The combination of anti-HER2 therapy and chemotherapy in women with HER2-positive disease has been shown to approximately halve the risk of recurrence and mortality compared with chemotherapy alone.
This type of treatment should be covered by the health system and made available to women as part of the standard therapy for HER2-positive breast cancer.
Some biosimilar products that are designed to be more affordable anti-HER2 options have been approved by the EMA as “biological substitutes” for trastuzumab. As these therapies are monoclonal antibodies and are created from living things, exact copies are not feasible. Biosimilars are deemed to be biologically similar to the original biological therapy.
Chemotherapy is recommended in the vast majority of women with triple-negative, HER2-positive breast cancers and in those with high-risk luminal-like HER2-negative tumours. Oestrogen-receptor-negative tumours show the most benefit from chemotherapy. The most common regimens are based on anthracyclines and taxanes.
A therapy of anthracycline followed by a taxane-based therapy regimen is the standard approach for most patients. This sequential use is more effective and less toxic than administering them together. The more common side effects of these treatments can be transitory, such as hair loss, or more lasting such as heart damage (cardiotoxicity) with anthracyclines and nerve damage (neuropathy) with taxanes.
Nonetheless, these therapy regimens reduce breast cancer mortality by about one-third. Chemotherapy can also be administered before surgery to reduce the size of the tumour. Women can request genomic testing of the tumour tissue to determine the genetic ‘signature’ of a cancer and the genetic risk profile. If it is found to be low risk, women may be spared the need for chemotherapy. (See the Genetic and Genomic Testing section)
Metastatic Breast Cancer
Women with metastatic breast cancer (MBC) should be treated by a multidisciplinary team, according to the latest evidence and guidelines (eg, the Advanced Breast Cancer (ABC) and ESO-ESMO guidelines). Testing of the new tumour site/sites should be performed because the characteristics (eg, hormone receptor status, HER2 status) may be different from the primary tumour.
The treatment approach may involve hormone therapy, anti-HER2 therapy or chemotherapy, depending on the tumour characteristics.
Newer targeted treatments are also showing some promise in metastatic disease, and include targets such as CDK 4/6 inhibition in hormone receptor-positive, HER2-negative MBC; and PARP inhibition in BRCA1/2-positive disease. Other novel approaches include immune checkpoint inhibitors, PIK3CA inhibitors, and tyrosine kinase inhibitors. For more on MBC see the Metastatic Breast Cancer section.
- ECIBC. European Quality Assurance Scheme for Breast Cancer Services
- ECIBC. International guidelines on breast cancer care
- European Breast Surgical Oncology Certification (BRESO)
- European Organisation for Research and Treatment of Cancer (EORTC)
- European Society of Breast Cancer Specialists (EUSOMA)
- European School of Oncology (ESO)
European Society of Medical Oncology. Early Breast Cancer: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up
- 5th ESO-ESMO International Consensus Guidelines For Advanced Breast Cancer (ABC 5)
- EBCC11 Manifesto 2018: Genetic risk prediction testing in breast cancer
- EBCC10 Manifesto 2016: Manifesto on breast centres/units
- EBCC9 Manifesto 2014: Manifesto on Optimal Pathology