1. Non Invasive (In Situ) Breast Cancer
   1. Lobular carcinoma in situ (LCIS)
   2. Ductal carcinoma in situ (DCIS)
   3. Paget's disease
2. Invasive Breast Cancer
   1. Invasive ductal carcinoma
   2. Invasive lobular carcinoma
   3. Locally advanced
   4. Inflammatory breast cancer (IBC)
   5. Metastatic breast cancer
3. Special Situations
   1. Breast cancer in men
   2. Breast cancer in pregnancy
   3. Phylloides tumour of the breast

1. Non Invasive (In Situ) Breast Cancer

Non-invasive (in situ) breast cancer refers to a cancer that is still within the milk duct and/or lobules of the breast. In other words, the cancer has not invaded through the walls of the milk ducts or lobules. The goal of treatment of in situ carcinoma is either preventing the occurrence of invasive disease or diagnosing the invasive component when it is still localized to the breast.

There are three types of non-invasive breast cancers:

• 1a. Lobular carcinoma in situ (LCIS) -"Lobular carcinoma in situ (Table 1) refers to cancer cells that have formed in the milk glands and are still confined there. This type of in situ cancer is often found in women around the age of menopause. LCIS is different from DCIS in that there is a high risk that the entire tissue of both breasts may develop cancer. Therefore, treatment of LCIS must be aimed at both breasts rather than just the affected one. LCIS is almost always hormonally positive."¹

Table 1. Lobular carcinoma in situ (LCIS)
Normal breast with lobular carcinoma in situ (LCIS) in an enlarged cross–section of the lobule. Breast profile: A: ducts B: lobules C: dilated section of duct to hold milk D: nipple E: fat F: pectoralis major muscle G: chest wall/ rib cage Enlargement: A: normal lobular cells B: lobular cancer cells C: basement membrane

Table content sourced with permission from www.breastcancer.org

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• 1b. Ductal carcinoma in situ (DCIS) - Ductal carcinoma in situ, also called intraductal cancer (Tables 2 and 3), refers to cancer cells that have formed in the mild ducts and are still confined there. The ducts become blocked and enlarged as cancer cells accumulate inside them. Calcium tends to collect in the blocked ducts and is visible on mammography as clustered or irregular calcifications (microcalcifications) on a screening mammogram in an otherwise asymptomatic woman.
  
  DCIS may present as nipple discharge or a palpable mass, usually also associated with mammographic calcifications. DCIS may also present as an incidental finding in a biopsy of a benign lesion. It accounts for 20-30% of the cancers found on screening mammograms.² If left untreated, DCIS may progress to form an invasive cancer with the potential for spreading throughout the body.
  
  DCIS occurs as two different cell types with one tending to progress to invasion more quickly than the other. The first type, which progresses more slowly, consist of smaller more normal-looking cells. These may be called solid (Table 4), papillary (Table 5) or cribiform (Table 6). The second type, called comedeonecrosis (Table 7), often progresses to invasion early in its growth and consists of large, irregular shaped cells. Because they are growing quickly, these cells tend to outgrow their supply of sugar and oxygen.³

Table 2. Ductal carcinoma in situ (DCIS)
Normal breast with non–invasive ductal carcinoma in situ (DCIS) in an enlarged cross–section of the duct. Breast profile: A: ducts B: lobules C: dilated section of duct to hold milk D: nipple E: fat F: pectoralis major muscle G: chest wall/rib cage Enlargement: A: normal duct cells B: ductal cancer cells C: basement membrane D: lumen (centre of duct)

Table content sourced with permission from www.breastcancer.org

Table 3. Range of ductal carcinoma in situ (DCIS)

Table 4. Solid cell growth sub-type
A: cancer cells B: basement membrane

Table content sourced with permission from www.breastcancer.org

Table 5. Cribiform cell growth sub-type
A: cancer cells B: basement membrane C: lumen (centre of duct)

Table content sourced with permission from www.breastcancer.org

Table 6. Papillary cell growth sub-type
A: cancer cells B: basement membrane C: lumen (centre of duct)

Table and image sourced with permission from www.breastcancer.org

Table 7. Comedo cell growth sub-type
A: living cancer cells B: dying cancer cells C: cell debris (necrosis) D: basement membrane

Table content sourced with permission from www.breastcancer.org

• 1c. Paget’s disease - Paget’s disease is a rare form of in situ cancer that can occur in a “pure” form but is often accompanied by an invasive cancer. Paget’s disease appears as reddish, itching, scaling or “eczema” of the nipple caused by cancer cells in the skin of the nipple and areola.⁴

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2. Invasive Breast Cancer

Invasive breast cancer refers to cells that have grown through the walls of the milk ducts and glands into the normal fatty tissue of the breast. The cells continue to grow causing a lump or thickening. They can then metastasize through the blood stream or lymphatic vessels to other parts of the body. The major types of invasive breast cancer are:

From Ducts and Glands

• 2a. Invasive (infiltrating) ductal carcinoma (IDC) – IDC is the most common and is also called mammary carcinoma or infiltrating ductal adenocarcinoma. (Table 8)
  • Type not otherwise specified (75%)
  • Tubular (1%)
  • Mucinous (1%)
  • Colloid (1%)
  • Medullary (1%)
• 2b. Invasive lobular carcinoma – Less common and difficult to diagnose on mammogram. Slightly higher risk of being in both breasts and are usually estrogen receptor positive. (Table 9)
  • Squamous carcinomas (less than 1%)
  • Mixed carcinomas (adenosquamous and metaplastic cancers) (less than 1%)⁵

Table 8. Invasive ductal carcinoma
Normal breast with invasive ductal carcinoma (IDC) in an enlarged cross–section of the duct. Breast profile: A: ducts B: lobules C: dilated section of duct to hold milk D: nipple E: fat F: pectoralis major muscle G: chest wall/ rib cage Enlargement: A: normal duct cells B: ductal cancer cells breaking through the basement membrane C: basement membrane

Table and image sourced with permission from www.breastcancer.org

Table 9. Invasive lobular carcinoma
Normal breast with invasive lobular carcinoma (ILC) in an enlarged cross–section of the lobule. Breast profile: A: ducts B: lobules C: dilated section of duct to hold milk D: nipple E: fat F: pectoralis major muscle G: chest wall/ rib cage Enlargement: A: normal cells B: lobular cancer cells breaking through the basement membrane C: basement membrane

Table and imaged sourced with permission from www.breastcancer.org

From other parts of the breast:

• Cystosarcoma phylloides (1%) - A type of sarcoma of the breast that may be benign or malignant depending on the number of dividing cells seen on pathology. These uncommon sarcomas of the female breast arise from the stromal elements. Histologically they may be categorized to be benign or malignant. Adenocarcinoma may co-exist and therefore pathology review of these tumours is recommended. A phylloides tumour should be suspected if a fibroadenoma is "recurrent." A pathology review at BC Cancer Agency may be helpful⁵
• Sarcomas (less than 1%) – These tumours come from connective tissue such as nerves, fat, fibrous tissue, or blood vessels of the breast
• Lymphomas (less than 1%)⁵

Other:

• 2c. Locally advanced breast cancer - Locally advanced breast cancer is cancer that is growing into the skin or chest wall or where there are enlarged lymph nodes that are matted together
• 2d. Inflammatory breast cancer (IBC) - IBC is a form of rapidly progressive locally advanced breast cancer characterized by symptoms that typically arise over weeks to months, not years: discoloration ranging from red to purple and affecting at least one third of the breast, thickening and/or fine dimpling, warmth, and a palpable ridge present at the margin of induration.⁶ It is often mistaken for a breast infection and is treated with antibiotics before a correct diagnosis is made. A biopsy of the affected skin often shows dermal lymphatic invasion by tumor cells. These tumour cells interfere with lymphatic drainage, thereby contributing to the clinical symptoms of IBC and presumably to its high rate of lymph node metastases.⁷
  
  IBC accounts for approximately 3-5% of all breast cancers.⁸ Almost all patients diagnosed with IBC will have lymph node involvement and about one third will have distant metastases at the time of diagnosis. Compared to other locally advanced breast cancers, IBC tends to have a younger age of onset, a worse prognosis and more ER negative tumours.⁶
  
  Inflammatory breast cancer is the most aggressive form of breast cancer with a median survival of 18 to 24 months, despite intensive combined modality treatment leading to a high initial response. Prompt initial referral to the BC Cancer Agency is suggested for these patients. Clinical trials are available and participation should be encouraged⁷
  
  
• 2e. Metastatic Disease - Metastatic disease of the breast (also known as distant or systemic recurrence) is when breast cancer cells have escaped into the blood stream prior to the first treatment. Some cancer cells can be resistant to adjuvant treatments and can grow and divide into detectable cancer metastases.⁹
  
  

  The most common sites for breast cancer to metastasize to are the bones, lungs, liver and brain. Other parts of the body that can be affected include the lymph nodes, skin, eyes, spinal cord, and ovaries.⁹

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3. Special Situations

• 3a. Breast cancer in men - Men develop breast cancer (about 1% of all breast cancers), but it is rare except in families with a BRCA2 gene mutation. The cancer usually appears as a lump under the nipple. Almost all male breast cancer is of ductal type and 90% of male breast cancers are estrogen receptor positive.¹⁰ Investigation of breast cancer in the male is identical to that of the female patient, including mammography as an initial investigation. A male’s likelihood of surviving breast cancer parallels that of a woman of the same age and stage of disease. Typically, men "present at a later stage than women, so overall, men with breast cancer fare less well than women."¹¹
  
  Because the male breast is very small, it is common for even small tumours to involve both skin and deep tissues, which affects prognosis. Surgery should include wide margins on both the skin and deep tissues and this may require removal of some underlying muscle. Axillary dissection is also required, therefore a modified radical mastectomy is often recommended.
  
  "Because of the small size of the male breast adjuvant radiotherapy is often recommended to reduce local recurrence. However the indications for post mastectomy radiation for males are essentially the same as those for females."¹⁰
  
  "There are no series of male patients which have been adequately studied in regard to adjuvant systemic therapy. However, experience demonstrates that the clinical behaviour of male and female breast cancers are very similar."¹¹ Currently, "adjuvant hormonal or chemotherapeutic recommendations are the same as for a woman of the same age and stage of disease. The role of aromatase inhibitors and fulvestrant in males has not been established."¹¹ Orchiectomy or LHRH may provide a response after progression on tamoxifen in metastatic disease.
  
  
• 3b. Breast cancer in pregnancy - Breast cancer occurring concurrent with pregnancy is an infrequent clinical event. "It is generally no more aggressive than breast cancer in non-pregnant women of the same age. The survival of women with breast cancer discovered during pregnancy is similar to survival of other women diagnosed at the same age. However, breast cancer in very young women (age less than 35 years) tends to be more difficult to cure and can be harder to diagnose"¹³, so they are most often lymph node positive and have a larger primary tumour size. "The diagnosis is often delayed because neither the patient nor the physician suspects malignancy."¹²
  
  Histologically, the tumours in pregnant women tend to be poorly differentiated, more frequently estrogen and progesterone receptor negative, and approximately 30% are HER2/neu positive.¹² Breast cancer does not spread to the fetus. Abortion of the fetus does not improve the outcome or have an effect on the growth of the mother’s cancer.¹²
  
  Patients should have a complete staging work-up, with proper shielding, pre-operatively. Whole body scans should be avoided.¹² The presence of metastatic disease may alter the treatment plan and influence the patient’s decision regarding maintenance of the pregnancy. Since radiation therapy is contraindicated during pregnancy, patients eligible for breast conserving surgery can only have it if radiation therapy can be delayed to the postpartum period.¹³
  
  Sentinel lymph node biopsy with radionuclide should be safe. There are limited data with only case reports and estimations of fetal radiation dose. Blue dye for sentinel node biopsy procedures is not recommended during pregnancy.¹²
  
  
• 3c. Phylloides tumours of the breast - These uncommon sarcomas of the female breast arise from the stromal elements. Histologically they may be categorized to be benign or malignant. Adenocarcinoma may co-exist and therefore pathology review of these tumours is recommended. Wide local excision (at least 2cm of histologically normal breast tissue margin and/or a clearly defined fascial boundary) is the treatment of choice for phylloides tumours. If the lesion is deep in the breast the excision must include fascia. Specimens should be linked so their margins can be assessed for involvement by tumour. A phylloides tumour should be suspected if a fibroadenoma is "recurrent". A pathology review at BC Cancer Agency may be helpful as lymph node metastases even in patients with "benign" disease. Metastases are generally to lung although bone and liver involvement may occur. Patients with more aggressive histology may be offered radiation therapy to improve local control rates. There is no known role for chemotherapy in the adjuvant setting.¹⁴

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REFERENCES:

1. Olivotto I, Gelmon K, McCready D, Pritchard K, Kuusk U. Intelligent patient guide to breast cancer. 4th ed. Edwards C, editor. Vancouver (BC): Intelligent Patient Guide Limited; 2006, pg.68-69.

2. Olivotto I, Gelmon K, McCready D, Pritchard K, Kuusk U. Intelligent patient guide to breast cancer. 4th ed. Edwards C, editor. Vancouver (BC): Intelligent Patient Guide Limited; 2006, pg. 66.

3. Olivotto I, Gelmon K, McCready D, Pritchard K, Kuusk U. Intelligent patient guide to breast cancer. 4th ed. Edwards C, editor. Vancouver (BC): Intelligent Patient Guide Limited; 2006, pg. 66, 68.

4. Olivotto I, Gelmon K, McCready D, Pritchard K, Kuusk U. Intelligent patient guide to breast cancer. 4th ed. Edwards C, editor. Vancouver (BC): Intelligent Patient Guide Limited; 2006, pg. 68.

5. Olivotto I, Gelmon K, McCready D, Pritchard K, Kuusk U. Intelligent patient guide to breast cancer. 4th ed. Edwards C, editor. Vancouver (BC): Intelligent Patient Guide Limited; 2006, pg. 71.

6. Harris JR, Lippman ME, Morrow M, Osbourne CK. Diseases of the breast. 3rd ed. Philadelphia, PA. Lippincott Williams & Wilkins; 2004, pg. 971.

7. BC Cancer Agency (http://www.bccancer.bc.ca). Vancouver (BC): 2006. (cited Sep 22, 2006). Available from: http://www.bccancer.bc.ca/HPI/CancerManagementGuidelines/Breast/Management/Inflammatory.htm

8. Olivotto I, Gelmon K, McCready D, Pritchard K, Kuusk U. Intelligent patient guide to breast cancer. 4th ed. Edwards C, editor. Vancouver (BC): Intelligent Patient Guide Limited; 2006, pg. 71.

9. Olivotto I, Gelmon K, McCready D, Pritchard K, Kuusk U. Intelligent patient guide to breast cancer. 4th ed. Edwards C, editor. Vancouver (BC): Intelligent Patient Guide Limited; 2006, pg.236-237.

10. Olivotto I, Gelmon K, McCready D, Pritchard K, Kuusk U. Intelligent patient guide to breast cancer. 4th ed. Edwards C, editor. Vancouver (BC): Intelligent Patient Guide Limited; 2006, pg. 255.

11. BC Cancer Agency (http://www.bccancer.bc.ca). Vancouver (BC): 2006. (cited Sep 22, 2006). Available from: http://www.bccancer.bc.ca/HPI/CancerManagementGuidelines/Breast/Management/CanceroftheMaleBreast.htm

12. Breast cancer: practice guidelines in oncology, Version 2.2006, 12-05-05 © 2005, National Comprehensive Cancer Network, Inc.

13. Olivotto I, Gelmon K, McCready D, Pritchard K, Kuusk U. Intelligent patient guide to breast cancer. 4th ed. Edwards C, editor. Vancouver (BC): Intelligent Patient Guide Limited; 2006, pg.247-248.

14. BC Cancer Agency (http://www.bccancer.bc.ca) Vancouver (BC): 2005 (cited Aug 25, 2005) http://www.bccancer.bc.ca/HPI/CancerManagementGuidelines/Breast/Management/Phylloides.htm

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