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Understanding Breast Cancer is reviewed approximately every two years. Check the This information was developed with help from health professionals .. inflammatory breast cancer and Paget's disease of the nipple. 8. Cancer Council .
Table of contents
- Understanding a Breast Cancer Diagnosis
- Understanding Breast Cancer Risk and How to Lower It
- Understanding Breast Cancer Diagnosis & Treatment
But before you decide what to do, research your options. Find a doctor you trust, and don't feel you have to rush to make a choice. The treatment options for breast cancer depend on the size of your tumor and how far it has spread in your body, your age, and how healthy you are. For most people, the first step is to remove breast cancer with surgery, followed usually by some mix of radiation therapy , chemotherapy , or hormone therapy. The standard surgery for breast cancer used to be the removal of the entire breast and lymph nodes nearby, called a modified radical mastectomy. But today, many women who find breast cancer before it has spread can remove just the lump.
This operation, called a lumpectomy , has proven to work just as well as a mastectomy , and the physical changes it causes are much less drastic. After this type of surgery, most women also get radiation therapy, chemotherapy , or hormone therapy. This treatment uses powerful drugs to kill cancer cells.
Your doctor might recommend it after you have surgery to kill any remaining cancer that the operation left behind. It helps reduce the chance that breast cancer will come back. Chemotherapy or hormone therapy are the main treatments for women whose cancer has spread to parts of the body outside of the breast and lymph nodes.
In this treatment, high-energy waves destroy cancer cells. Doctors usually give radiation therapy after a lumpectomy and sometimes after a mastectomy to reduce the risk of cancer coming back in the same breast. The treatments generally start a few weeks after the surgery so the area has some time to heal. They can last for several days or a few weeks. The type of radiation that most people know about is called external beam radiation.
A machine focuses a beam of radiation on the tumor. It's the most common type of radiation therapy for breast cancer. The other type is called brachytherapy. It delivers radiation to the cancer through radioactive seeds or pellets -- as small as grains of rice -- that doctors place inside the breast near the cancer.
You can get brachytherapy by itself or with external beam radiation. Tumor size, location, and other things determine if this type of radiation is right for you. After a mastectomy, reconstructive plastic surgery can replace breast tissue that doctors had to remove along with the cancer, including skin and the nipple. The goal of reconstruction is to give the two breasts the same size and shape again. You might get breast implants , or doctors can move tissue from other parts of your body to your breast.
Hormone therapy, also called endocrine therapy, blocks your body's natural hormones from reaching the cancer cells that use them. These were significant discoveries because in the s it was demonstrated that breast tumors grew in response to estrogen, which intensified the quest for antiestrogen drugs. Scientists at the British pharmaceutical company AstraZeneca first synthesized a drug called tamoxifen in to exploit its contraceptive effects .
However, tamoxifen was later found to exert antiestrogen effects in estrogen receptor-positive breast cancers. It functions by blocking the binding of estrogen to the estrogen receptor. However, because the drug was also shown stimulate estrogen activity in the endometrium, it is considered as a partial antiestrogen and therefore classified as a selective estrogen receptor modulator SERM . Following a series of clinical trials in humans, the Food and Drug Administration FDA approved tamoxifen for the treatment of metastatic estrogen receptor-positive breast cancer in The FDA later approved tamoxifen as adjuvant therapy for post-menopausal women and for prophylactic use in women at high risk of breast cancer .
The s and beyond saw a spike in research and development in breast cancer. By that time, it was clear through familiar clustering that first-degree relatives of affected individuals were at a higher risk of developing breast cancer. Substantial developments in molecular biology and genetics accelerated in the s. This momentum culminated in numerous genetic discoveries, notably the publication of the identification of the variants of two main breast cancer-associated genes, BRCA1 and BRCA2, published in Science in by Easton et al.
Understanding a Breast Cancer Diagnosis
Families with a history of both breast and ovarian cancers are usually associated with inherited BRCA1 mutations, whereas families that include male breast cancer cases are more commonly linked to BRCA2 mutations. This protein was the first receptor tyrosine kinase discovered by Stanley Cohen et al. The neu oncogene was cloned, sequenced and mapped to human chromosome 17 . In , Slamon et al. In William Muller et al. It was clear at this point that HER2 amplification was oncogenic in breast cancers.
In , Axel Ullrich and his colleagues at Genentech showed that a monoclonal antibody directed against the extracellular domain of HER2 specifically inhibited the growth HER2-positive breast cancer cells. Phase III was started in and closed in In a fast-track process in , the FDA approved Herceptin in combination with paclitaxel as a first-line treatment of HER2-positive metastatic breast cancers, and as a single agent for second and third-line therapy.
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Research in cancer biology in the s and s led to significant progress in cancer prevention, early detection, and treatment. More was learned about cancer in these two decades than in the past centuries. Cancer research in the new millennium is developing on many fronts. Progress in the understanding of the pathology and molecular biology, as well as the genetic alterations underlying breast cancer development and progression in the 21st century have led to the pathological and molecular classification of breast cancer and development of new genetic tests, for instance, and enabled scientists to develop novel therapeutic drugs and strategies for this disease.
Understanding Breast Cancer Risk and How to Lower It
This project steered the genomic revolution, and molecular technologies have diversified since This has opened up strategies to study cancer and discover novel and more effective diagnostic and therapeutic tools for the disease. Several cancer databases were created in the first decade of the 21st century.
For instance, the Cancer Genome Atlas TCGA project, founded in the United States in , uses large-scale genome sequencing and bioinformatics to catalogue cancer-related mutations, which has improved our understanding of the molecular basis of cancer http: The molecular classification of breast cancer based on gene expression profiles reported by a few research groups in the first decade of the 21st century is one of the momentous developments in personalized medicine in recent years.
Genome-wide profiling technologies have led to a better understanding of the biological heterogeneity of breast cancer.
Gene expression profiling of human breast tumors revealed molecular subtypes with distinct gene signatures and associated clinical outcomes  ,  ,  , . In Perou et al. All these subtypes are histologically different and tend to vary in their clinical outcomes.
The luminal A subtype, for example, is typically histologically low-grade and has the most favorable prognosis, whereas luminal B cancers are often high-grade and therefore more aggressive. HER2-positive cancers are usually high-grade and are associated with poor prognosis. The basal-like tumors are usually the most aggressive and are associated with the shortest relapse-free and overall survival .
Some TNBCs lack the gene expression profile of the basal-like tumors and are classified as normal-like breast cancers. Normal-like breast tumors are usually small and tend to have a more favorable prognosis . Claudin-low is a more recently described class of breast cancer that is often triple-negative, but distinct in that it expresses low levels of cell-cell junction proteins including claudin and E-cadherin Reviewed by .
All these gene profiling studies have drastically altered our conceptualization of breast cancer and provided a multitude of translational research opportunities to improve diagnosis, prognostic and therapeutic approaches for this disease.
This edition included definitions of new histopathological diagnosis classifications complemented by recent descriptions of molecular subtypes, as well as genetics, prognostic and predictive features . The test results display a Recurrence Score ranging from 0 to , where the higher the score, the greater the chances of relapse if a patient is treated with hormonal therapy alone. Thus, with this test, oncologists can identify patients who are in urgent need of lifesaving chemotherapy to prevent cancer recurrence.
Low risk patients who do not need additional chemotherapy are thus spared the related side effects and unnecessary additional costs. Other tumor-based gene expression-based prognostic models have been developed . This test would generally spare many older breast cancer patients adjuvant treatments . Tamoxifen therapy is usually the first treatment for ER-positive patients with locally advanced or metastatic breast cancer.
As described earlier, tamoxifen possesses some estrogenic activity, which may cause endometrial hyperplasia or carcinoma and may also predispose patients to thrombosis. Fulvestrant however is essentially a pharmacological antagonist and not a partial agonist like tamoxifen. The drug is a selective estrogen receptor down-regulator SERD so named because it binds directly to the ER, preventing ER dimerization and promoting the rapid degradation of the receptor .
The ovaries are the principal source of estradiol estrogen in premenopausal women . However, in postmenopausal women the ovaries cease to produce estrogen, and the synthesis of estrogens occurs in a number of extragonadal sites including the adipose tissue of the breast . Estrogens are synthesized in postmenopausal women mainly via conversion of adrenal androgens to estrone and estradiol with estradiol being the predominant physiological hormone.
Aromatase is an enzyme that catalyzes the rate-limiting and final step of this estrogen biosynthesis. Aromatase Inhibitors AIs block the function of this enzyme, thus limiting the supply of estrogen that fuels the growth of some breast cancers . AIs have been shown to be more effective than the antiestrogen tamoxifen in reducing the risk of breast cancer recurrence and spread, and are well tolerated.
Letrozole produced by Norvatis was first approved for long-term use in post-menopausal women who have completed five years of tamoxifen treatment. Clinical trials revealed that the drug reduces the risk of breast cancer recurrence and spread even more than tamoxifen alone. Anastrazole produced by AstraZeneca and marketed under the trade name Arimidex is another FDA-approved AI that was shown to improve survival and alleviate the symptoms of cancer for post-menopausal women with advanced breast cancer . Raloxifene , a drug that had been used to prevent and treat osteoporosis in postmenopausal women since , was later shown to be as effective as tamoxifen in reducing the risk of developing invasive breast cancer.
Raloxifene also functions by blocking the effects of estrogen on breast tissue, but cannot, however, be used to treat invasive breast cancer or to decrease the risk of developing breast cancer . HER2 is a receptor tyrosine kinase that transmits signals to promote several cellular processes including cell proliferation. The drug was also approved for use in combination with the drug capecitabine for patients with advanced breast cancer whose tumors overexpressed the HER2 protein. In , lapatinib was also approved as an initial therapy in combination with letrozole for patients with HER-2 positive breast cancer Reviewed in .
The general consensus from these studies was that the use of preventive surgery significantly reduces the risk of breast cancer as well as the risk of ovarian and fallopian tube cancers . Eventually, the so-called Angelina Jolie effect followed, which led to a general increase in referrals to centers for genetic tests . This helped alleviate some of patients' insecurities associated with the loss of their sexual identity post-preventative surgery.
The Angelina Jolie effect has underscored the significant impact of a celebrity announcement in the health care sector. The obvious side effects of mastectomy along with salpingo-oophorectomy for pre-menopausal women are early-onset menopause and infertility. The combination of pertuzumab with Herceptin and docetaxel, as first-line treatment for HER2-positive metastatic breast cancer, has been found to substantially slow cancer growth and significantly improve progression-free survival as compared with combining a placebo with Herceptin and docetaxel.
Because the use of this regimen was not associated with any serious side effects, this combination therapy represents substantial progress in the standard of care for HER2-positive patients  , . Additional follow-up studies further supported the positive benefit-to-risk ratio in HER2-positive metastatic breast cancer patients treated with the pertuzumab, Herceptin, and docetaxel regimen  , .
Understanding Breast Cancer Diagnosis & Treatment
The result of this study has fueled momentum into research exploring the effectiveness of combining two or more drugs that target the same signaling pathway. T-DM1, also known by its trade name Kadcyla developed by Genentech is a conjugation of two anticancer drugs — the HER2-targeted trastuzumab T and the chemotherapy drug emtansine, which binds to microtubules and inhibits cell division. The action of DM1 is coupled with the anti-tumor activities of trastuzumab, which include antibody-dependent cell-mediated cellular cytotoxicity and inhibition of ligand-independent intracellular HER2 signaling events that promote cell proliferation .
Protein-bound nanoparticle technology is also used now in most cancers. Abraxane delivery spares patients from the side effects such as severe allergic reactions associated with solvent-delivered taxol. The therapeutic options for breast cancer patients have increased dramatically in the 21st century with increasing efforts towards the development of more efficient and effective screening, diagnosis and treatment options. The landscape of therapy for patients with metastatic breast cancer is also changing.
For instance, many ongoing studies are exploring strategies to overcome endocrine resistance, target TNBC and develop new anti-HER2 therapies. There are promising advances in immunotherapy and new directions in inhibiting aberrant angiogenesis, one of the hallmarks of tumors . Our understanding of the molecular characteristics of tumors in general, coupled with better screening methods has helped shape the recent advances in breast cancer treatment. Neoadjuvant therapy, for example, has become a standard recourse.
Therefore, chemotherapy is still viewed as the clinical state of the art therapy . Many cancers, including breast cancer, are driven by a subset of cells termed cancer stem cells. These are tumor-initiating cells that can initiate tumor growth as well as mediate tumor metastasis. Several signaling pathways, such as the STAT3 signaling pathway, are known to regulate breast cancer stem cell BCSC self-renewal and may therefore be considered as viable therapeutic targets .
Advances in high-throughput genomic profiling have enabled researchers to catalogue the spectrum of somatic alterations in breast cancers. Genomic profiling will be valuable for precision and individualized medicine through accurate diagnosis, prognosis, stratification and better dynamic monitoring of treatment response.
Several other therapeutic strategies have attracted attention recently. Some of the recent technological improvements have provided more tools in the fight against breast cancer. These new techniques include marginally invasive treatments such as radiofrequency ablation  and cryo-ablation .
These technologies are still in their infancy; more research and long-term data collection should clarify their effectiveness. Current targeted therapies for breast cancer include the use of tamoxifen, fulvestrant and aromatase inhibitors for ER-positive breast cancers, and Herceptin and various HER2 inhibitors for the treatment of HER2-positive breast cancers.
Numerous chemotherapeutic drugs have also been approved as adjuvant and neoadjuvant treatment of all breast cancer subtypes including TNBCs. Unfortunately, most patients treated with these drugs eventually develop resistance, often leading to enhanced disease progression and death. Drug resistance is a common manifestation of cancer and is a major factor in the failure of many forms of chemotherapy. The mechanisms underlying drug resistance are poorly understood. This therefore represents a major clinical deficit, especially in the case of a heterogeneous disease like breast cancer wherein a plethora of intrinsic and acquired mechanisms may favor drug resistance.
Differential expression of non-coding RNAs in tamoxifen-resistant and aromatase inhibitors-resistant breast cancer cells indicates that microRNAs could be potential therapeutic targets in endocrine-resistant tumors . Research to identify and block these alternative pathways is part of a concerted effort by researchers and clinicians to overcome drug resistance in all cancers including breast cancer reviewed in  , . Breast cancer is heterogeneous in nature at both the epidemiological and molecular levels.
Clinical and epidemiological evidence has identified many important breast cancer risk factors such as age, family history, early menarche and medical history; factors which are intangible or beyond our control. These include obesity, lack of exercise, smoking, drinking, and diet, along with factors that may negatively influence a woman's hormonal environment such as hormone replacement therapy HRT and reproductive history. These rate-limiting steps in the fight against breast cancer must not be overlooked. As highlighted in this review, appreciable growth in the knowledge of cancer biology has led to remarkable progress in the early detection, treatment and prevention of cancers in recent years.
The increasing focus on tailored therapy and the integration of cancer stem cell-based targeted therapies and immune therapies, together with existing therapeutic methods, hold promise for the cure of breast cancer. The author is unaware of any affiliations, memberships, or financial holdings that might be perceived as affecting the objectivity of this review. The author thanks Raghuveera Goel graduate student, Lukong lab for his critical review of the manuscript. The author apologizes to those whose work was not included owing to space limitations. The author also thanks The Beatles for inspiring the title.
The Transparency document associated with this article can be found, in online version. National Center for Biotechnology Information , U. Published online Jan This article has been cited by other articles in PMC. Scope of review The increased incidence and awareness of breast cancer has led to significant changes in diagnosis and treatment in recent decades. Major conclusions Breast cancer remains a serious public health issue worldwide.
General significance Tracing the history of breast cancer, highlights how increased awareness of the disease, and progress in research and development have enhance our understanding of the disease. Learn about your personal risk and ways to take an active role in your breast health. Read about being a survivor, or offering support to a breast cancer survivor.
Find local resources available to assist you. Becoming informed and empowered is the first step in battling this disease.
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Know about your personal risks and ways to take an active role in your breast health.