Breast Cancer

Introduction

Lung, female breast and colorectal cancer account for one-third of the world's cancer incidences.[1] When looking at cancer mortality across the globe female breast cancer is ranked 5th in terms of mortality.[1] However, with the advances in both the diagnostic and treatment approaches for breast cancer survival rate after a diagnosis of breast cancer has significantly improved.[2] The increase in the number of breast cancer survivors has resulted in more research and care being directed toward developing interventions that will help improve the overall quality of life for women who have survived breast cancer.[3] Physiotherapists have an important role in the rehabilitation process during and after a diagnosis of breast cancer, as well as in the care of survivors.

What is Breast Cancer?

Mammograms showing a normal breast (left) and a cancerous breast (right)

Breast cancer involves the production of malignant cells in the breast.[4] These cells grow uncontrollably affecting nearby tissue and/or spreading to other parts of the body through a process called metastasis.[4]

However, not all cell growth in breast tissue is malignant.[4] Non-cancerous conditions such as atypical hyperplasia cysts and abscesses, and non-cancerous tumours such as intraductal papillomas can form.[4]

Breast cancers are usually adenocarcinomas.[4] These tumours develop in the following two locations within the breast:[4]

  1. The cells that line the milk ducts (also known as ductal carcinoma)[4]
  2. The milk-producing glands (also known as lobular carcinoma)[4]

Ductal and lobular carcinomas can each be classified as in-situ or invasive (infiltrating).[5] With in-situ, there is no growth into surrounding tissues (the cancer is confined within the ducts or lobules).[5] With invasive, the malignant cells that started in the ducts or glands have begun to invade the surrounding tissue and potentially other parts of the body.[5]

As previously mentioned, metastasis involves the spread to one or more sites elsewhere in the body. This occurs by way of directly affecting an organ or travelling through the lymphatic and/or circulatory systems.[6]

The following terms can be utilized to gage how far the malignant cells have spread:[7]

  • Localized means there is no spread.[7]
  • Regional means there is spread to the lymph nodes, tissues, or organs close to where cancer started (the primary site).[7]
  • Distant (also known as metastatic cancer) means there is spread to organs or tissues that are farther away from the primary site.[7] The main sites of metastasis for breast cancer include bones, lungs, brain, and liver.[8]

Other types of breast cancer are not nearly as common as the adenocarcinomas.[4] They include the following:[4]

  • Inflammatory breast cancer[4]
  • Paget disease of the nipple[4]
  • Triple negative breast cancer[4]

Staging

The system commonly used to classify the extent of breast cancer is the AJCC/TNM system.[4][5] The TNM system uses information on tumour size and how far it has spread within the breast and nearby organs (T), lymph node involvement (N), and the presence or absence of distant metastases (M).[5] Once the T, N, and M are determined through stage grouping, a stage of 0, I, II, III, or IV is assigned.[4][5] The stage number and degree of cancer spread are positively correlated.[4][5]

Click here to review the stages of breast cancer.

Prevalence

Breast cancer can occur in both men and women. However, it is quite rare in men; it accounts for 1% of cancers[9][10][11][12][13][14] and 0.2% of cancer-related deaths in men.[15][16] One in 8 women will develop invasive breast cancer in their lifetime and approximately 1 in 33 will die from it.[17] In 2018, approximately 2.1 million women received a diagnosis of breast cancer.[18] This makes it the most commonly diagnosed cancer and the second leading cause of cancer-related deaths in women.[6] Throughout the decades, the incidence of breast cancer has increased in some countries.[18] The reason for this may be due to a combination of advances in screening and diagnosis, as well as increased rates of obesity and fewer child births per woman.[18]

Survivorship varies across the globe, such that 5-year relative survival was ≥80% in the United States, Canada, and Austria, but <40% in Denmark, Poland, and Algeria.[19] This may be attributed to differences in diagnostics and treatments,[20][21][22][23] as well as a lack of healthcare resources in some countries.[24][25] Verdecchia et al (2008)[26] found that gross domestic product, total national expenditure on health, and the number of computed tomography (CT) scanners per million were correlated with cancer survival. 

Breast cancer-related lymphedema (BCRL) is condition that a woman can develop anytime 3-20 years after treatment.[27] The incidence varies and likely depends on the type of treatment received. For example, 12 months post-treatment 12-26% of women had BCRL.[28][29] Recent evidence suggests that 1 in 5 women will acquire it at some point.[30]

Risk Factors

  • Increased age: Older age has been shown to increase the risk of developing breast cancer.[31][32] Between 2013 and 2015, the probability of a woman developing breast cancer in the United States between birth to 49 years of age was 1 in 51; the probability increased when ≥70 years of age to 1 in 15.[31]
  • Sex (females > males)
  • Personal history of breast cancer
  • Family history of breast cancer: In comparison to women who have do not have a family history of breast cancer, one first-degree relative has been found to lead to a 1.75-fold higher risk and 2 first-degree relatives has been found to lead to a 2.5-fold higher risk of developing breast cancer.[33]
  • Breast cancer associated genes 1 and 2 (BRCA1 and BRCA2) mutations: BRACA1 and BRCA2 are responsible for the suppression of tumours.[34] Furthermore, mutations of these genes have been shown to increase the risk of developing breast cancer.[35]
  • Dense breasts
  • Alcohol consumption: Alcohol has been shown to be a risk factor for the development of breast cancer.[36][37][38][39] 10 g more of alcohol per day may increase the risk by approximately 7.1%.[38]
  • Obesity: Obesity, especially in postmenopausal women, has been found to increase the risk of developing breast cancer.[40] (30 and 31)
  • Cigarette smoking: There is no consensus in the evidence that cigarette smoking increases the risk of developing breast cancer, which may be partly because of the correlation between smoking and alcohol consumption.[41] An analysis[38] found no significant difference between smokers and non-smokers.[38] However, Terry and colleagues (2002)[42] found that those who smoked more and for longer were at a higher risk, especially if they smoked 20 or more cigarettes per day over the course of 40 years or more.[42]
  • Race: Non-hispanic white woman show higher incidence of breast cancer.[43] African-American, Hispanic, Native American, and Asian woman show a higher mortality rate.[43]
  • Menstrual history: A menstrual period that starts early and ends later in life may increase the risk of developing breast cancer.[32]
  • Child birth: Having children after the age of 30 or not having any children at all may increase the risk of developing breast cancer.
  • Endogenous and exogenous estrogens: Exogenous estrogens normally come from oral contraceptives and hormonal replacement therapy.[44] A combined oral contraceptive, one that includes both estrogen and progesterone, may increase the risk of the development of breast cancer, but this increased risk did not remain 10 years after stopping the pill.[41][45] In the UK, the Million Women Study found an increased risk in the development of breast cancer after using estrogen and progesterone combinations in hormone replacement therapy.[46] However, this risk did not remain 2 years after stopping hormone replacement therapy.[47]

See The National Cancer Institute Breast Cancer Risk Assessment Tool

Clinical Presentation

Breast cancer may be asymptomatic and undetectable in its earlier stages. The hallmark signs and symptoms of a ductal carcinoma are a lump in the breast and breast tenderness (not usually pain). The hallmark signs and symptoms of a lobular carcinoma do not involve a lump. There is often a change in breast texture. Therefore, a lobular carcinoma may be harder to detect.[48]

Other signs and symptoms of breast cancer may include the following:[4]

  • Change in breast shape or size[4]
  • Unusual discharge from the nipple[4]
  • Lump in armpit[4]
  • Retraction inwards or inversion of the nipple[4]

Late signs and symptoms of breast cancer may include the following:[4]

  • Bone pain[4]
  • Weight loss[4]
  • Nausea[4]
  • Loss of appetite[4]
  • Jaundice[4]
  • Shortness of breath[4]
  • Cough[4]
  • Headache[4]
  • Double vision[4]
  • Muscle weakness[4]

A useful mnemonic to help remember some of the signs of breast cancer is B.R.E.A.S.T.[49]

Breast mass[49]

Retraction[49]

Edema[49]

Axillary mass[49]

Scaly nipple[49]

Tender breast. [49]
Breast cancer incidence by anatomical site (females).svg.png

Breast Self Examination


There does not seem to be a consensus on whether or not breast self examinations (BSE) should be carried out by women.[50] In fact, the Canadian Taskforce on Preventive Health Care and the American Cancer Society (ACS) no longer recommend BSE.

Allen et al (2010)[51] commented on the potential benefits and harms of BSE. Some of the benefits included that BSE increase a woman's sense of comfort and autonomy with their health and breasts, the tool is non-invasive, lumps can be palpated, and women become more aware of breast changes over time.[51] Some of the harms included the potential for increased usage of the healthcare system and its resources (more cost, biopsies, etc), as well as higher levels of anxiety depression.[51] Furthermore, women should speak with their physicians to discuss whether the benefits of BSE outweigh the risks for that individual and that they seek clarity on how to perform the examination.

In conclusion, it remains important that women become familiar with the appearance and feel of their breasts. Any changes that may be detected can be reported to a physician for further investigation.

Diagnosis

  • Mammography: A mammogram provides an x-ray of the breast tissue. Mammograms are typically suggested for women every year after they turn 40. It is recommended that women who are at a higher risk for breast cancer should talk with their doctors about an appropriate screening plan for them.[52][53]
  • Ultrasound: An ultrasound may be performed if a lump is suspected, and this test creates a picture of the tissue within the breast. Ultrasounds can help determine if the area in question is a cyst or a solid lump.[52][53]
  • Magnetic Resonance Imaging (MRI): A MRI may provide a more detailed look at the breast tissue compared to a mammogram or ultrasound. MRIs are move expensive, but may show a lump that the other test did not pick up on previously.[52][53]Women who are at higher risk are recommended to not only receive yearly mammograms,but should also receive a yearly MRI. Ultimately though women should discuss the appropriate screening process with their doctor.[54]
  • Biopsy: A biopsy is a procedure that is performed to detect whether the breast tissue that has been removed is cancerous or not. This test gives a definite answer whether cancer is present. A or not biopsy is suggested if there is an area within the breast that is questionable for cancer.[52][53] Hormone Receptor Tests If someone is diagnosed with breast cancer, hormone receptor tests can be used to help develop treatment options. If the cancerous tissue is positive for hormone receptors (estrogen and/or progesterone) then hormone therapy is a recommended form of treatment.[52][53]
  • HER2/neu Test: HER2 is the human epidermal growth factor receptor-2, which is a protein that can sometimes be found on cancer cells. The cancer cells that contain the HER2/neu protein tend to be more aggressive and may have a less favourable prognosis. If this is the case, then a targeted approach to that specific area will be used as a treatment option.[52][53][55] 

Factors that May Reduce Breast Cancer Risk

  • Breastfeeding
  • Participating in moderate or vigorous activity
  • Maintaining a healthy body weight [56]

Systemic Involvement

Breast cancer that has metastasized can be manifested in several ways[53][49].

  • Bone: is the most frequent site of metastasis in both men and women and symptoms can include back hip or shoulder pain, and/or pain with weight-bearing.
  • Central Nervous System: is another frequent site for metastasizes of breast cancer, especially at the thoracic levels of the spinal cord. Signs and symptoms that are associated with neurologic involvement include unilateral upper extremity numbness and tingling (cervical/thoracic), leg weakness or paresis (lumbar), or bowel and bladder symptoms (sacral). Other common sites of metastases are lymph nodes, lung, brain, and liver, as well as the remaining breast tissue. Neurologic involvement can also be manifested in a paraneoplastic syndrome, which is a term used to describe associated signs and symptoms at a site that is distant from the tumour and/or metastasis.
  • Paraneoplastic syndromes often present in ways that seem uncorrelated with cancer and may mimic disorders of the endocrine, metabolic, hematologic, or neuromuscular systems. Clinical signs and symptoms can accompany a relatively limited increase in the size of cancer and therefore may provide early clues to the presence of cancer. Stiff-man syndrome is an example of a paraneoplastic syndrome that affects women with breast cancer and is characterized by progressive symptoms of neuropathy (nerve damage) or myelopathy (spinal cord damage). Increased muscle tone and rigidity in the spine and lower extremities (especially the ankle dorsiflexors) are commonly experienced.
    Musculoskeletal and integumentary involvement, as they relate to breast cancer prior to treatment, have been previously discussed in the section on Characteristics/Clinical Presentation.

Management

Treatment for breast cancer depends on the severity and stage of disease that the patient is in at the time. In many cases there is a typical sequence that is followed.

Surgery

Surgery is usually the first step in treatment of breast cancer. The goal of surgery is to remove the cancerous tumor by either removing the entire breast (mastectomy) or removing only the lump and surrounding tissue (lumpectomy). Other forms of surgery such as breast reconstruction and lymph node removal can be done when necessary. After surgery is performed the patient may receive chemotherapy and/or radiation therapy.  A retrospective review shows that in comparison to subcutaneous mastectomy with implant procedure, the partial mastectomy with mini latissimus dorsi flap procedure produces significantly superior body image and cosmetic outcomes. It can also be a treatment of choice in selected patients with small breasts and a high tumor/breast ratio[57].

Chemotherapy

Chemotherapy is used to destroy the remaining cancer cells that may be left within the body. This form of treatment is applied to the whole body through the blood stream. Chemotherapy can be used with all stages of breast cancer, but is especially recommended for those patients in which the cancer has spread.

Radiation Therapy

Radiation therapy is typically used for early stages (can be used in all stages) of breast cancer following a lumpectomy. This form of treatment targets a more specific area unlike chemotherapy. Radiation therapy may also be used following chemotherapy.

Hormonal Therapy

Once the following treatment options have been completed hormonal therapy may be advised. Hormonal therapy works by decreasing estrogen amounts and blocking its action on the breast cancer cells. The doctor and the patient will discuss each specific case and decide on the best treatment options.[52][54]

[58]
[59]
[60]

Medications

Medications for the treatment of breast cancer most often include chemotherapy drugs and hormone replacement drugs. Chemotherapy medications are many times used in combinations of two or three at a time. Two common groups include anthracyclines and taxanes. Anthracyclines such as, Epirubicin and Doxorubicin, are similar to antibiotics that destroy the cancer cells’ genetic material. Taxanes such as, Paclitaxel and Docetaxel, on the other hand interfere with how the division of the cancer cells.[54]  Paclitaxel and Docetaxel are both categorized as plant alkaloid anticancer drugs. Each are given intravenously and used mostly to treat solid tumors involving breast and ovarian cancers. Toxicities are common in cancer treatment and each drug is not alike. The acute toxicity of Docetaxel is hypersensitivity and a rash and delayed toxicity results in neurotoxicity, fluid retention, neutropenia, alopecia, and bone marrow depression.[55] Hormone therapies such as the drug Tamoxifen stop the growth, spread, or recurrence of ER-positive tumors by preventing estrogen from reaching the tumors. Tamoxifen is a mixed estrogen antagonist and agonist that blocks the estrogen activation in the breast and decreases growth factors in the breast tissue. The side-effects are similar to postmenopausal symptoms: hot flashes, nausea, irregular menses, vaginal bleeding and weight gain, as well as slightly increasing a woman's risk for endometrial cancer.[61] Tamoxifen is the most common drug used for premenopausal women to help prevent the recurrence of breast cancer and another drug, Toremifene is the newer estrogen receptor antagonist that is being used in cases of advanced breast cancer.[53][55] Tamoxifen also appears to have a preventive effect in women with a high risk of breast cancer and has now been approved as a chemopreventive agent in this population. [55]

Drug Warning: Cancer patients who receive the targeted therapy bevacizumab (Avastin) in combination with chemotherapy are at increased risk of serious side effects that may lead to death, according to a meta-analysis of 16 clinical trials that was conducted by researchers at Stony Brook University School of Medicine in New York.[62] Fatal events, most commonly hemorrhaging, only occurred in 2.5% of the participants receiving the Avastin treatment compared to those not receiving (1.7% of fatality). The approximated 50% increase in risk occurred in patients also prescribed platinum or taxane chemotherapy agents such as carboplatin and paclitaxel. The results were published in a meta-analysis by Rapura and colleagues (2011).[62]

Newly FDA Approved Drug: Treatment with eribulin (Halaven™) improved overall survival in women with metastatic breast cancer whose disease progressed despite multiple rounds of prior chemotherapy, according to the results of a phase III clinical trial called EMBRACE. Based on these findings, the FDA approved eribulin last November for women with metastatic disease who have already undergone at least two previous chemotherapy regimens. Eribulin is a laboratory-made form of halichondrin B, a substance derived from a sea sponge. It targets the protein tubulin cells (building blocks of microtubules (narrow, hollow tubes inside a cell), involved in cell division and cell movement), although it binds to tubulin in a different way, interfering with cancer cell division and growth. Women receiving eribulin lived 2.5 months longer than women treated with their physician’s drug of choice and had equal side effects of neutropenia, leucopenia, and peripheral neuropathy.[63]

Physical Therapy Management

After treatment for breast cancer, women may experience any of the following impairments that can be addressed by a physical therapist:

  • Decreased strength of the upper extremity
  • Decreased shoulder mobility
  • Scar tightness (breast and/or axilla)  
  • Upper extremity ache 
  • Lymphedema of the upper extremity
  • Neuropathic pain  
  • Musculoskeletal pain (breast, axilla, and/or neck-shoulder) 
  • Chronic pain  

Karki and colleagues (2005)[64] researched the effects that impairments have on activity limitations and participation restrictions in 96 women at 6- and 12-month follow-ups after an operation for breast cancer. Severity of the impairments were measured using a modified Visual Analogue Scale (VAS).[64] Activity limitations and sleep function were measured using the Behavioural Rate Scale for Patients with Breast Cancer.[64] Results showed increased impairment severity with upper extremity lifting and carrying, as well as sleep disturbances, regardless of the type of operation.[64] While the prevalence decreased at the 12-month follow-up, changes were not statistically significant.[64] Results also show that women experience constant restrictions at home, work, and during leisurely activities, which may also have a negative impact on their social health.[64]

Aerobic exercise, such as walking, cycling, or swimming, has been shown to decrease cancer-related fatigue,[65][66][67] improve quality of life,[68][69] reduce cognitive impairments associated with various cancer therapies,[70] improve cardiovascular outcomes,[71] and improve sleep dysfunction.[72] Research suggests that treadmill exercises provide cardioprotective effects on the Doxorubicin-induced cardiotoxicity.[73] 

Cantarero-Villanueva and colleagues (2011)[74] carried out an 8-week multimodal physiotherapy program, which was comprised of aerobic exercises, core stability exercises, and some recovery with stretching and myofascial release techniques.[74] The researchers found statistically significant improvements in strength, suggesting that core stability exercises should not be ignored in women who have undergone treatment for breast cancer.[74] In fact, chemotherapy has been found to lead to even more muscle atrophy.[75] The protocol that Cantarero-Villanueva and colleagues (2011)[74] followed can be seen in the table below.

Other muscle groups that should be targeted include the rotator cuff, serratus anterior, trapezius, rhomboids, biceps, and pectoralis muscles.[76] Exercises can begin with an elastic bands and be performed 2x/week for 2 sets of 10-15 repetitions.[77] However, it is also important to observe the individual's scapulohumeral rhythm and supplement the exercise program with neuromuscular facilitation exercises if it needs to be corrected.[78][79] This study aimed to analyze the effects of types of surgery and hormone therapy on muscle strength in breast cancer survivors suggested that breast cancer survivors should be encouraged to perform supervised strength training programs for different muscle groups to improve strength[80].

Several forms of manual therapy can be carried out by a physical therapist to address certain impairments. They include the following:

  • Joint mobilization techniques
  • Soft tissue release techniques
  • Neurodynamic techniques

Also see page on Lymphedema for treatment of BCRL.

Differential Diagnosis

There are several other conditions that may be associated with breast pain other than breast cancer itself.  Mastodynia, mastitis, benign tumors/cysts, and Paget's disease are some examples of conditions that may cause a patient to present with breast pain resembling breast cancer.

  1. Mastodynia: is an irritation of the upper dorsal intercostal nerve. This type of breast pain may be associated with ovulatory cycles.
  2. Mastitis: this occurs in lactating women that is an inflammatory condition. The breast may become red, swollen, painful, and/or warm. This is a result of the mammary duct becoming obstructed and clogged.[49]
  3. Benign Tumors/Cysts: These include fibroadenomas, cysts, and calcifications within the breast. When lumps within the breast are unchanged and have been present for many years this is often times a benign and hormonally induced. Other benign lumps include, papillomas, fat necrosis, and mammary duct ectasia. The patient would need to be referred to their doctor to differentiate these conditions.[49]
  4. Paget's Disease: This is a disease of the breast not to be confused with Paget's disease of the bone. It is a rare condition of ductal carcinoma which arises from the ducts near the nipple. Symptoms may include, redness, itching, and flaking of the nipple.[49]

Resources

You can visit some of the websites listed below for more resources.

Download a PDF on Oncology and Breast Cancer

References

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